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Keywords = exon 20 mutations

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11 pages, 2393 KB  
Article
Small Cell Transformation of EGFR-Mutant NSCLC Treated with Tyrosine Kinase Inhibition
by Adam Rock, Isa Mambetsariev, Siddhika Pareek, Jeremy Fricke, Xiaochen Li, Javier Arias-Romero, Waasil Kareem, Leonidas Arvanitis, Debora S. Bruno, Stacy Gray and Ravi Salgia
Curr. Oncol. 2025, 32(10), 554; https://doi.org/10.3390/curroncol32100554 - 3 Oct 2025
Viewed by 221
Abstract
Introduction: Epidermal growth factor receptor (EGFR) alterations exist in 15–50% of non-small cell lung cancer (NSCLC) diagnoses. Although effective therapeutics have been developed in the form of tyrosine kinase inhibitors (TKI), various mechanisms of resistance lead to treatment failure after exposure to EGFR [...] Read more.
Introduction: Epidermal growth factor receptor (EGFR) alterations exist in 15–50% of non-small cell lung cancer (NSCLC) diagnoses. Although effective therapeutics have been developed in the form of tyrosine kinase inhibitors (TKI), various mechanisms of resistance lead to treatment failure after exposure to EGFR TKI-based therapy. Of these, histologic transformation (HT) into small cell lung cancer (SCLC) represents approximately 14% of cases. Methods: Within a single institution, we retrospectively reviewed longitudinal data from both tissue and liquid biopsies of patients with histologic transformation after a diagnosis of EGFR-mutant NSCLC. We sought to further characterize the baseline and emergent genomic alterations after HT to SCLC in the context of TKI exposure, along with germline alterations that may contribute to lineage plasticity and outcomes. Results: Fifteen patients were included in our analysis. Of these, EGFR exon 19 deletions were the most frequent (n = 11, 73.3%), followed by L858R (n = 3, 20%) and L861Q (n = 1, 6.7%). The median time for transformation was 17 months (95%CI, 8.9–41.9 months). The median OS of our cohort was 51.6 months (95%CI, 26.3—NE) with a median OS post-transformation of 13.4 months. Recurrent genomic alterations included TP53, Rb1, PIK3CA, and BRAF. Germline testing revealed a pathogenic alteration in FBN1, with a recurrent variant of unknown significance (VUS) in PALLD. Conclusion: Post-transformation somatic mutation testing and germline testing at presentation revealed unique mutational profiles not previously reported in the setting of HT to SCLC. Further investigations are required to determine the optimal treatment and sequencing following HT. Full article
(This article belongs to the Section Thoracic Oncology)
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21 pages, 630 KB  
Article
Hormone Receptor Positive/HER2 Negative Breast Carcinoma: Association of PIK3CA Mutational Status with PD-L1 and Tumor Cell Microenvironment and Their Prognostic Significance
by Danijel Lopac, Emina Babarović, Justin Hagen, Petra Valković Zujić, Damir Grebić and Ita Hadžisejdić
Int. J. Mol. Sci. 2025, 26(19), 9489; https://doi.org/10.3390/ijms26199489 - 28 Sep 2025
Viewed by 181
Abstract
Novel research data in different cancer types indicate that mutations within PIK3CA might serve as a biomarker of an improved response to immune therapy. Therefore, the aim of this study was to evaluate and examine possible differences in the tumor microenvironment composition and [...] Read more.
Novel research data in different cancer types indicate that mutations within PIK3CA might serve as a biomarker of an improved response to immune therapy. Therefore, the aim of this study was to evaluate and examine possible differences in the tumor microenvironment composition and PD-L1 expression as well the prognostic significance of CD4, CD8, CD68, and CD163 in PIK3CA mutated and non-mutated hormone receptor positive and HER2 negative (HR+/HER2−) breast carcinoma. Breast carcinoma tissue was analyzed by Cobas PIK3CA mutation test for the presence of PIK3CA mutation and immunohistochemistry was applied to assess PD-L1 expression and CD4, CD8, CD68, and CD163 infiltration within tumor. Statistically significant association was observed between PD-L1 expression and the presence of PIK3CA exon 20 mutation (p = 0.044), with PD-L1–positive patients predominantly harboring this mutation. Tumors harboring PIK3CA mutations exhibited moderate to strong statistically significant positive correlations between PD-L1 expression and infiltration by CD8 cells (rs = 0.462, p = 0.0027), CD68 cells (rs = 0.398, p = 0.0134), and CD163 cells (rs = 0.617, p < 0.0001). In patients with PIK3CA mutation and exon 20 PIK3CA mutation there was statistically significant longer survival without recurrence (p = 0.026 and p = 0.041, respectively). Research regarding PD-L1 expression, immune cells and PIK3CA mutations might have an impact on how to determine therapeutic approaches for patients with HR+/HER2− breast carcinoma. Full article
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16 pages, 1522 KB  
Article
Evaluation of PD-L1 Expression and Anti-EGFR Therapy in EGFR-Mutant Non-Small-Cell Lung Cancer
by Gizem Teoman, Elanur Karaman, Şafak Ersöz and Sevdegül Aydın Mungan
Medicina 2025, 61(8), 1467; https://doi.org/10.3390/medicina61081467 - 15 Aug 2025
Viewed by 1022
Abstract
Background and Objectives: Non-small-cell lung cancer (NSCLC) often has epidermal growth factor receptor (EGFR) mutations, which are key targets for therapy. EGFR mutation subtypes, especially exon 19 deletions and exon 21 L858R mutations, influence responses to EGFR tyrosine kinase inhibitors [...] Read more.
Background and Objectives: Non-small-cell lung cancer (NSCLC) often has epidermal growth factor receptor (EGFR) mutations, which are key targets for therapy. EGFR mutation subtypes, especially exon 19 deletions and exon 21 L858R mutations, influence responses to EGFR tyrosine kinase inhibitors (TKIs) and patient survival. Despite progress in TKI treatments, resistance and different responses remain challenges. This study explores the relationship between EGFR mutation subtypes, PD-L1 expression, and patient outcomes after anti-EGFR therapy. Materials and Methods: We studied 176 cases of EGFR mutation-positive NSCLC. Next-generation sequencing was used to analyze EGFR and other mutations, while PD-L1 expression was evaluated through immunohistochemistry. We analyzed EGFR mutation subtypes, PD-L1 status, treatments, and survival outcomes. Results: Among 176 cases, 88.6% were adenocarcinomas. Within the EGFR mutation spectrum, exon 19 deletions were the most common subtype, accounting for 40.9% of cases, followed by the point mutation in exon 21, which occurred in 35.8% of cases. Less frequent alterations, making up 23.3% of all detected mutations, included mutations in exon 18, insertions, and point mutations such as S768I and T790M in exon 20, as well as changes in exon 2, exon 7, and other less frequently affected regions. Exon 19 mutations were associated with older age, female sex, adenocarcinoma, and bone metastasis (p < 0.05). TP53 was the most common concurrent mutation (44.3%). PD-L1 positivity (TPS ≥ 1%) was observed in 48.3%, with high expression (TPS ≥ 50%) in 25.9%. Exon 21 mutations were significantly linked to PD-L1 negativity (p = 0.008). The median overall survival was longest with TKI therapy (51 months), and this was also observed in PD-L1-positive patients, although the difference was not statistically significant. The median progression-free survival for patients treated with TKIs and those with EGFR mutations was 14 months. PD-L1-positive patients receiving TKIs had significantly longer survival than those who did not (51 vs. 17 months, p = 0.003). Conclusions: EGFR mutation subtypes and PD-L1 expression seem to affect treatment outcomes and survival in NSCLC. The observed links emphasize the potential value of combining molecular and immunological markers to guide therapy choices. Full article
(This article belongs to the Section Pulmonology)
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14 pages, 909 KB  
Article
The -124C>T Mutation of the TERT Promoter Indicates Favorable Prognosis in Ovarian Clear Cell Carcinoma: A Single Institutional Study in China
by Xiaonan Zhou, Yifei Liu, Jue Hu, Jing Zhang, Min Ren, Gang Ji, Xu Cai and Rui Bi
Curr. Oncol. 2025, 32(8), 422; https://doi.org/10.3390/curroncol32080422 - 27 Jul 2025
Viewed by 899
Abstract
Background: Ovarian clear cell carcinoma (OCCC) is characterized by chemoresistance and poor prognosis in advanced or recurrent cases. This study aimed to find specific prognostic markers for OCCC. Methods: We analyzed 169 OCCC patients for clinicopathological features. TERT promoter and PIK3CA mutations were [...] Read more.
Background: Ovarian clear cell carcinoma (OCCC) is characterized by chemoresistance and poor prognosis in advanced or recurrent cases. This study aimed to find specific prognostic markers for OCCC. Methods: We analyzed 169 OCCC patients for clinicopathological features. TERT promoter and PIK3CA mutations were assessed by Sanger sequencing, and immunohistochemistry for ARID1A, HDAC6, Cyclin E1, and p53 was performed on tissue microarrays. Survival analysis was conducted using Kaplan–Meier and Cox regression models. Results: The -124C>T TERT promoter mutation was associated with longer OS and PFS and was an independent predictor of favorable OS. This mutation correlated with lower CA125 levels and higher SNP frequency. p53 mutations indicated advanced disease, bilateral tumors, reduced Cyclin E1, and poor prognosis. Low HDAC6 expression was linked to worse PFS. Mutual exclusivity was observed between PIK3CA exon 20 mutations and SNPs. Conclusions: The -124C>T TERT promoter mutation may serve as a favorable prognostic marker in OCCC, while p53 mutations and reduced HDAC6 expression are associated with poor outcomes. Full article
(This article belongs to the Section Gynecologic Oncology)
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16 pages, 3903 KB  
Article
Identification of Salt Tolerance-Related NAC Genes in Wheat Roots Based on RNA-Seq and Association Analysis
by Lei Zhang, Aili Wei, Weiwei Wang, Xueqi Zhang, Zhiyong Zhao and Linyi Qiao
Plants 2025, 14(15), 2318; https://doi.org/10.3390/plants14152318 - 27 Jul 2025
Viewed by 639
Abstract
Excavating new salt tolerance genes and utilizing them to improve salt-tolerant wheat varieties is an effective way to utilize salinized soil. The NAC gene family plays an important role in plant response to salt stress. In this study, 446 NAC sequences were isolated [...] Read more.
Excavating new salt tolerance genes and utilizing them to improve salt-tolerant wheat varieties is an effective way to utilize salinized soil. The NAC gene family plays an important role in plant response to salt stress. In this study, 446 NAC sequences were isolated from the whole genome of common wheat and classified into 118 members based on subgenome homology, named TaNAC1 to TaNAC118. Transcriptome analysis of salt-tolerant wheat breeding line CH7034 roots revealed that 144 of the 446 TaNAC genes showed significant changes in expression levels at least two time points after NaCl treatment. These differentially expressed TaNACs were divided into four groups, and Group 4, containing the largest number of 78 genes, exhibited a successive upregulation trend after salt treatment. Single nucleotide polymorphisms (SNPs) of the TaNAC gene family in 114 wheat germplasms were retrieved from the public database and were subjected to further association analysis with the relative salt-injury rates (RSIRs) of six root phenotypes, and then 20 SNPs distributed on chromosomes 1B, 2B, 2D, 3B, 3D, 5B, 5D, and 7A were correlated with phenotypes involving salt tolerance (p < 0.0001). Combining the results of RT-qPCR and association analysis, we further selected three NAC genes from Group 4 as candidate genes that related to salt tolerance, including TaNAC26-D3.2, TaNAC33-B, and TaNAC40-B. Compared with the wild type, the roots of the tanac26-d3.2 mutant showed shorter length, less volume, and reduced biomass after being subjected to salt stress. Four SNPs of TaNAC26-D3.2 formed two haplotypes, Hap1 and Hap2, and germplasms with Hap2 exhibited better salt tolerance. Snp3, in exon 3 of TaNAC26-D3.2, causing a synonymous mutation, was developed into a Kompetitive Allele-Specific PCR marker, K3, to distinguish the two haplotypes, which can be further used for wheat germplasm screening or marker-assisted breeding. This study provides new genes and molecular markers for improvement of salt tolerance in wheat. Full article
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20 pages, 3781 KB  
Article
Ginsenoside Rg3 Adjunctively Increases the Efficacy of Gefitinib Against NSCLC by Regulating EGFR Copy Number
by Xinyi Lv, Yuehan Song, Tianhua Liu, Dingdan Zhang, Xinpeng Ye, Qingqing Wang, Rongrong Li, Jiayi Chen, Shujing Zhang, Xue Yu and Chunying Hou
Pharmaceuticals 2025, 18(7), 1077; https://doi.org/10.3390/ph18071077 - 21 Jul 2025
Viewed by 712
Abstract
Background: Lung cancer has the highest morbidity and mortality of all tumors, and the development of TKI drugs targeting EGFR activating mutations has brought lung cancer treatment into the targeted era. In view of their low efficacy and susceptibility to drug resistance, [...] Read more.
Background: Lung cancer has the highest morbidity and mortality of all tumors, and the development of TKI drugs targeting EGFR activating mutations has brought lung cancer treatment into the targeted era. In view of their low efficacy and susceptibility to drug resistance, there is an urgent need to find strategies to increase their efficacy and reduce the incidence of drug resistance. Methods: In this study, we examined the distribution and probability of EGFR mutations in non-small cell lung cancer patients in the cBioPortal database and compared the survival prognosis of patients with normal and abnormal EGFR, NSCLC patients treated with and without TKI, and NSCLC patients with different EGFR gene copy numbers. We established a mouse lung cancer model and examined the histomorphological characteristics of lung tissues via hematoxylin and eosin staining. Additionally, changes in the copy number of the EGFR gene and its protein expression levels were detected using RT-qPCR and Western blotting. Furthermore, we quantified the concentration of the EGFR protein using ELISA. Results: We found no significant advantage of EGFR-TKI therapy over first-line chemotherapeutic agents in patients with EGFR-abnormal NSCLC. The reason for this may be related to the abnormal EGFR gene copy number; the higher the copy number increases, the worse the survival prognosis of the patients. In molecular biology experiments, we demonstrated that ginsenoside Rg3 down-regulated the copy number of 18, 19, 20, and 21 exons and protein expression of EGFR in lung adenocarcinoma cells. The results of in vivo pharmacodynamic assays confirmed that sequential administration of ginsenoside Rg3 with TKI drugs could achieve a gainful complementary effect. Conclusions: Ginsenoside Rg3 down-regulates the copy number of EGFR important exons in EGFR-mutant cells of lung adenocarcinoma and reduces EGFR protein expression, thus providing a high gainful complementary effect in combination with EGFR-TKI. Full article
(This article belongs to the Topic Advances in Anti-Cancer Drugs: 2nd Edition)
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12 pages, 603 KB  
Case Report
First Successful Fertility Preservation Using Oocyte Vitrification in Patient with Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy
by Yuka Tanaka, Bunpei Ishizuka and Kazuhiro Kawamura
Endocrines 2025, 6(3), 31; https://doi.org/10.3390/endocrines6030031 - 1 Jul 2025
Viewed by 651
Abstract
Background/Objectives: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder caused by mutations in the AIRE gene. Approximately 60% of affected females develop premature ovarian insufficiency (POI) by age 30, often most commonly due to steroidogenic autoantibodies. Although APECED is typically diagnosed in [...] Read more.
Background/Objectives: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder caused by mutations in the AIRE gene. Approximately 60% of affected females develop premature ovarian insufficiency (POI) by age 30, often most commonly due to steroidogenic autoantibodies. Although APECED is typically diagnosed in childhood, its reproductive implications are underrecognized. This study reports a case of successful fertility preservation in an adult woman with APECED and reviews the relevant literature. Methods: We describe the clinical course of a 37-year-old woman with genetically confirmed APECED who underwent ovarian stimulation for fertility preservation. A comprehensive PubMed search was also conducted to identify English-language case reports on fertility preservation in APECED-associated POI. Results: The patient experienced menarche at age 13, adrenal insufficiency at 14, and menstrual irregularities from age 18. Genetic analysis confirmed an AIRE mutation (NM_000383: exon 11: c.1400+1G>A). Given her relatively high anti-Müllerian hormone level, she opted for fertility preservation and underwent six cycles of ovarian stimulation, resulting in the cryopreservation of 17 mature oocytes. During ovarian stimulation, multiple follicular developments were observed, but serum E2 levels remained low. The literature review identified fewer than 20 reported cases addressing fertility preservation in APECED, highlighting its rarity and the lack of standardized management. Conclusions: Although APECED frequently leads to early POI due to impaired steroidogenesis, residual ovarian function may persist. Early assessment of ovarian reserve and timely fertility counseling are crucial, even in asymptomatic patients or those diagnosed in childhood. Reproductive planning should be integrated into the long-term care of women with APECED. Full article
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9 pages, 1523 KB  
Brief Report
Replication of Missense OTOG Gene Variants in a Brazilian Patient with Menière’s Disease
by Giselle Bianco-Bortoletto, Geovana Almeida-Carneiro, Helena Fabbri-Scallet, Alberto M. Parra-Perez, Karen de Carvalho Lopes, Tatiana de Almeida Lima Sá Vieira, Fernando Freitas Ganança, Juan Carlos Amor-Dorado, Andres Soto-Varela, Jose A. Lopez-Escamez and Edi Lucia Sartorato
Genes 2025, 16(6), 654; https://doi.org/10.3390/genes16060654 - 28 May 2025
Viewed by 854
Abstract
Ménière’s Disease (MD) is a chronic inner ear disorder defined by recurring episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and/or fullness in the ear. Its prevalence varies by region and ethnicity, with scarce epidemiological data in the Brazilian population. Although most MD [...] Read more.
Ménière’s Disease (MD) is a chronic inner ear disorder defined by recurring episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and/or fullness in the ear. Its prevalence varies by region and ethnicity, with scarce epidemiological data in the Brazilian population. Although most MD cases are sporadic, familial MD (FMD) is observed in 5% to 20% of European cases. Through exome sequencing, we have found a rare missense variant in the OTOG gene in a Brazilian individual with MD with probable European ancestry (chr11:17599671C>T), which was previously reported in a Spanish cohort. Two additional rare missense heterozygous OTOG variants were found in the same proband. Splice Site analysis showed that chr11:17599671C>T may lead to substantial changes generating exonic cis regulatory elements, and protein modelling revealed structural changes in the presence of chr11:17599671C>T, chr11:17576581G>C, and chr11:17594108C>T, predicted to highly destabilize the protein structure. The manuscript aims to replicate genes previously reported in a Spanish cohort, and the main finding is that a Brazilian patient with MD also has variants previously reported in familial MD, supporting OTOG as the most frequently mutated gene in MD. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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7 pages, 3451 KB  
Case Report
Combination of Osimertinib and Brigatinib in the Treatment of EGFR Triple-Mutated Lung Adenocarcinoma: A Case Report
by Daphnée Demers and Marie Florescu
Curr. Oncol. 2025, 32(5), 270; https://doi.org/10.3390/curroncol32050270 - 7 May 2025
Viewed by 952
Abstract
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in treating patients with EGFR-mutated non-small-cell lung cancers (NSCLCs), especially in cases with secondary resistance mutations. However, tertiary resistance mutations often arise, and there is currently no established [...] Read more.
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used in treating patients with EGFR-mutated non-small-cell lung cancers (NSCLCs), especially in cases with secondary resistance mutations. However, tertiary resistance mutations often arise, and there is currently no established standard of care for NSCLC harboring triple EGFR mutations. In recent years, brigatinib, an anaplastic lymphoma kinase (ALK) TKI, has shown effectiveness in treating EGFR triple-mutated NSCLC. Despite this, the combined use of osimertinib and brigatinib remains largely unstudied. This case report describes a 51-year-old woman with EGFR-mutated NSCLC who was initially treated with first- and second-generation EGFR TKIs, then switched to osimertinib upon development of an exon 20 T790M mutation. When an exon 20 C797S mutation emerged, the decision was made to add brigatinib to the osimertinib regimen. The combined treatment of osimertinib and brigatinib offers a promising new approach. Nonetheless, it is important to consider the potential risk of off-target toxicities. Full article
(This article belongs to the Section Thoracic Oncology)
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12 pages, 1305 KB  
Article
Unraveling Survival Determinants in Patients with Advanced Non-Small-Cell Lung Cancer with EGFR Exon 20 Insertions
by Kung-Yang Wang, Shih-Chieh Chang, Yu-Feng Wei, Jui-Chi Hung, Chung-Yu Chen and Cheng-Yu Chang
Curr. Oncol. 2025, 32(3), 174; https://doi.org/10.3390/curroncol32030174 - 18 Mar 2025
Viewed by 1394
Abstract
Background: Lung cancer is the leading cause of cancer-related death in Taiwan. It is often associated with mutations in the epidermal growth factor receptor (EGFR) gene, with common mutations accounting for approximately 85% of all EGFR-related cases. However, the remaining [...] Read more.
Background: Lung cancer is the leading cause of cancer-related death in Taiwan. It is often associated with mutations in the epidermal growth factor receptor (EGFR) gene, with common mutations accounting for approximately 85% of all EGFR-related cases. However, the remaining 15% are caused by uncommon mutations in EGFR, mainly insertions in exon 20 (about 4%). The response to EGFR tyrosine kinase inhibitors (TKIs) can vary markedly with exon 20 insertions. However, few prior large-scale studies have examined patients with these EGFR mutations. Methods: This study combines the databases of several large hospitals in Taiwan to analyze the effects and clinical significance of rare EGFR mutations on responses to EGFR-TKIs, considering the changes in medication. Results: This study enrolled 38 patients with non-small-cell lung cancer and EGFR exon 20 insertions. It assessed the correlations of various predictors with progression-free survival (PFS) and overall survival (OS). It showed that among those with EGFR exon 20 insertions, the median PFS was 5.15 months, and OS reached 13 months. The median PFS was 5.4 months for afatinib, 5.7 months for chemotherapy, and 4.3 months for first-generation EGFR-TKIs. Conclusions: EGFR-TKIs may be considered as an alternative treatment option for patients with EGFR exon 20 insertions in cases where the currently recommended therapies, such as chemotherapy with or without amivantamab, are either unavailable or intolerable. The potential use of afatinib for specific patients in this context depends on the precise characteristics of their mutation and remains to be determined. Full article
(This article belongs to the Section Thoracic Oncology)
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12 pages, 1428 KB  
Article
First-Line Pyrotinib Combination Therapy for HER2-Mutated Advanced NSCLC: A Retrospective Cohort Analysis
by Yan Xiang, Meiling Zhang, Qian Wang, Jingwen Liu, Lulin Zeng, Ao Sun and Kaihua Lu
Curr. Oncol. 2025, 32(3), 148; https://doi.org/10.3390/curroncol32030148 - 4 Mar 2025
Viewed by 1740
Abstract
Background: HER2 mutations are rare driver events in advanced NSCLC, with limited relief from current targeted therapies. This study aimed to characterize the molecular features of HER2-mutant NSCLC and to evaluate the clinical efficacy of pyrotinib-based combination therapy as a first-line treatment, providing [...] Read more.
Background: HER2 mutations are rare driver events in advanced NSCLC, with limited relief from current targeted therapies. This study aimed to characterize the molecular features of HER2-mutant NSCLC and to evaluate the clinical efficacy of pyrotinib-based combination therapy as a first-line treatment, providing evidence for optimizing treatment strategies. Methods: NSCLC patients diagnosed at Jiangsu Province People’s Hospital from 2016 to 2024 were enrolled. HER2-positive cases were screened by IHC/FISH and further profiled by NGS. Treatment response was assessed by RECIST 1.1, and survival analysis was performed using Kaplan–Meier and log-rank tests. Results: Among 144 HER2-mutant NSCLC cases confirmed by NGS, 10 insertion mutations, 26 missense mutations, and 2 fusion mutations were identified. The most common mutation was the exon 20 p.A775_G776insYVMA (47.9%), and TP53 was the most frequent co-mutation (10.4%). In terms of efficacy, the pyrotinib-based combination therapy demonstrated significant clinical benefit, with an ORR of 33.3%, DCR of 95.2%, median PFS (mPFS) of 11.3 months (95% CI: 10.27–12.26), and median OS (mOS) of 21.0 months (95% CI: 18.00–23.94). Subgroup analysis revealed no significant impact of mutation subtype or co-mutation status on the treatment efficacy, but patients with brain metastases had a significantly worse prognosis than those without metastasis (mPFS: 5.1 vs. 12.9 months, p < 0.01; mOS: 9.3 vs. 26.5 months, p < 0.01). All TRAEs were grade 1–3 (any grade: 90.5%; grade 3: 14.3%), with the most common TRAE being diarrhea (any grade: 85.7%; grade 3: 9.5%). Conclusions: Pyrotinib-based combination therapy is a feasible first-line treatment for HER2-mutant NSCLC, demonstrating significant survival benefits and manageable toxicity. However, brain metastasis patients require enhanced comprehensive management. Full article
(This article belongs to the Section Thoracic Oncology)
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14 pages, 1463 KB  
Article
Investigation of Microvascular Involvement Through Nailfold Capillaroscopic Examination in Children with Familial Mediterranean Fever
by Fatih Kurt, Belkız Uyar, Muferet Erguven and Sengul Cangur
Medicina 2025, 61(2), 264; https://doi.org/10.3390/medicina61020264 - 4 Feb 2025
Viewed by 1163
Abstract
Background and Objectives: Familial Mediterranean fever (FMF) is a lifelong autoinflammatory disease characterized by episodes of fever and aseptic polyserositis. Commonly associated with vasculitis, FMF’s impact on microcirculation was investigated by examining nailfold capillaries using capillaroscopy. Materials and Methods: This study included 32 [...] Read more.
Background and Objectives: Familial Mediterranean fever (FMF) is a lifelong autoinflammatory disease characterized by episodes of fever and aseptic polyserositis. Commonly associated with vasculitis, FMF’s impact on microcirculation was investigated by examining nailfold capillaries using capillaroscopy. Materials and Methods: This study included 32 female and 28 male FMF patients diagnosed according to the Tel Hashomer and Yalçınkaya criteria and a control group of 20 female and 10 male age-matched cases. Demographic characteristics, medical history (abdominal pain, fever, chest pain, and joint pain), and physical examination findings of the cases were assessed. FMF gene mutations, acute-phase reactants, urine analysis, and spot urine protein/creatinine ratios were evaluated. Nailfold capillaries were examined via capillaroscopy by the same dermatology specialist. Results: There was no significant age or gender difference between groups. The most common symptoms in the case group were abdominal pain (81.7%) and joint pain (65%). Pathological findings in capillaroscopy, such as microhemorrhages and avascular areas, were significantly more frequent in the FMF case group (p < 0.001; p < 0.001). Physiological findings, including hairpin-shaped capillaries and shortened loops, were significantly more common in the control group (p = 0.001; p = 0.034). No significant relationships were found between kidney involvement, subclinical inflammation, presence of microhemorrhages and avascular areas in capillaroscopy, and disease duration. Additionally, no significant differences were observed in capillaroscopic findings between those with exon-10 mutations in the MEFV gene and those with non-exon-10 mutations. Conclusions: In conclusion, our study demonstrated secondary microvascular findings due to inflammation in FMF patients using capillaroscopy, a cost-effective and safe tool. Full article
(This article belongs to the Section Hematology and Immunology)
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13 pages, 1707 KB  
Article
Characterization of CK2, MYC and ERG Expression in Biological Subgroups of Children with Acute Lymphoblastic Leukemia
by Luca Lo Nigro, Marta Arrabito, Nellina Andriano, Valeria Iachelli, Manuela La Rosa and Paola Bonaccorso
Int. J. Mol. Sci. 2025, 26(3), 1076; https://doi.org/10.3390/ijms26031076 - 26 Jan 2025
Cited by 1 | Viewed by 1217
Abstract
Despite the excellent survival rate, relapse occurs in 20% of children with ALL. Deep analyses of cell signaling pathways allow us to identify new markers and/or targets promising more effective and less toxic therapy. We analyzed 61 diagnostic samples collected from 35 patients [...] Read more.
Despite the excellent survival rate, relapse occurs in 20% of children with ALL. Deep analyses of cell signaling pathways allow us to identify new markers and/or targets promising more effective and less toxic therapy. We analyzed 61 diagnostic samples collected from 35 patients with B- and 26 with T-ALL, respectively. The expression of CK2, MYC and ERG genes using Sybr-Green assay and the comparative 2-ΔΔCt method using 20 healthy donors (HDs) was evaluated. We observed a statistically significant difference in CK2 expression in non-HR (p = 0.010) and in HR (p = 0.0003) T-ALL cases compared to HDs. T-ALL patients with PTEN-Exon7 mutation, IKZF1 and CDKN2A deletions showed high CK2 expression. MYC expression was higher in pediatric T-ALL patients than HDs (p = 0.019). Surprisingly, we found MYC expression to be higher in non-HR than in HR T-ALL patients. TLX3 (HOX11L2)-rearranged T-ALLs (27%) in association with CRLF2 overexpression (23%) showed very high MYC expression. In B-ALLs, we detected CK2 expression higher than HDs and MYC overexpression in HR compared to non-HR patients, particularly in MLL-rearranged B-ALLs. We observed a strong difference in ERG expression between pediatric T- and B-ALL cases. In conclusion, we confirmed CK2 as a prognostic marker and a therapeutic target. Full article
(This article belongs to the Special Issue Acute Leukemia: From Basic Research to Clinical Application)
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20 pages, 2383 KB  
Article
Molecular and Biochemical Mechanisms of Scutellum Color Variation in Bactrocera dorsalis Adults (Diptera: Tephritidae)
by Guangli Wang, Weijun Li, Jiazhan Wu, Ye Xu, Zhaohuan Xu, Qingxiu Xie, Yugui Ge, Haiyan Yang and Xiaozhen Li
Insects 2025, 16(1), 76; https://doi.org/10.3390/insects16010076 - 14 Jan 2025
Viewed by 1240
Abstract
Bactrocera dorsalis (Hendel) is an invasive fruit and vegetable pest, infesting citrus, mango, carambola, etc. We observed that the posterior thoracic scutella of some B. dorsalis adults are yellow, some light yellow, and some white in China. Compared with the B. dorsalis races [...] Read more.
Bactrocera dorsalis (Hendel) is an invasive fruit and vegetable pest, infesting citrus, mango, carambola, etc. We observed that the posterior thoracic scutella of some B. dorsalis adults are yellow, some light yellow, and some white in China. Compared with the B. dorsalis races with a yellow scutellum (YS) and white scutellum (WS), the race with a light-yellow scutellum (LYS) is dominant in citrus and carambola orchards. To reveal genetic correlates among the three races, the genomes of 22 samples (8 with YS, 7 with LYS, and 7 with WS) were sequenced by high-throughput sequencing technology. Single-nucleotide polymorphism (SNP) annotation showed that there were 17,580 non-synonymous mutation sites located in the exonic region. Principal component analysis based on independent SNP data revealed that the SNPs with LYS were more similar to that with YS when compared with WS. Most genes associated with scutellum color variation were involved in three pathways: oxidative phosphorylation, porphyrin and chlorophyll metabolism, and terpenoid backbone biosynthesis. By comparing the sequences among the three races, we screened out 276 differential genes (DGs) in YS vs. WS, 185 DGs in LYS vs. WS, and 104 DGs in YS vs. LYS. Most genes determining color variation in B. dorsalis scutella were located on chromosomes 2–5. Biochemical analysis showed that β-carotene content in YS and LYS was significantly higher than that in WS at any stage of adult days 1, 10, and 20. No significant differences were observed in cytochrome P450 or melanin content in YS, LYS, or WS. Our study provides results on aspects of scutellum color variation in B. dorsalis adults, providing molecular and physiological information for revealing the adaptation and evolution of the B. dorsalis population. Full article
(This article belongs to the Section Insect Pest and Vector Management)
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Article
Detection of KMT2A Partial Tandem Duplication by Optical Genome Mapping in Myeloid Neoplasms: Associated Cytogenetics, Gene Mutations, Treatment Responses, and Patient Outcomes
by Qing Wei, Shimin Hu, Jie Xu, Sanam Loghavi, Naval Daver, Gokce A. Toruner, Wei Wang, L. Jeffrey Medeiros and Guilin Tang
Cancers 2024, 16(24), 4193; https://doi.org/10.3390/cancers16244193 - 16 Dec 2024
Cited by 8 | Viewed by 2035
Abstract
KMT2A partial tandem duplication (PTD) involves intragenic KMT2A duplications and has been associated with poorer prognosis. In this study, we evaluated KMT2A PTD in 1277 patients with hematological malignancies using optical genome mapping (OGM). KMT2A PTD was detected in 35 patients with acute [...] Read more.
KMT2A partial tandem duplication (PTD) involves intragenic KMT2A duplications and has been associated with poorer prognosis. In this study, we evaluated KMT2A PTD in 1277 patients with hematological malignancies using optical genome mapping (OGM). KMT2A PTD was detected in 35 patients with acute myeloid leukemia (AML) (7%), 5 patients with myelodysplastic syndrome (MDS) (2.2%), and 5 patients with chronic myelomonocytic leukemia (CMML) (7.1%). The PTDs varied in size, region, and copy number. An Archer RNA fusion assay confirmed KMT2A PTD in all 25 patients tested: 15 spanning exons 2 to 8 and 10 spanning exons 2 to 10. Most patients exhibited a normal (n = 21) or non-complex (n = 20) karyotype. The most common chromosomal abnormalities included loss of 20q or 7q and trisomy 11/gain of 11q. All patients had gene mutations, with FLT3 ITD and DNMT3A prevalent in AML and DNMT3A and RUNX1 common in MDS and CMML. Among patients who received treatment and had at least one follow-up bone marrow evaluation, 82% of those with de novo AML achieved complete remission after initial induction chemotherapy, whereas 90% of patients with secondary or refractory/relapsed AML showed refractory or partial responses. All but one patient with MDS and CMML were refractory to therapy. We conclude that OGM is an effective tool for detecting KMT2A PTD. Neoplasms with KMT2A PTD frequently harbor gene mutations and display normal or non-complex karyotypes. Patients with KMT2A PTD are generally refractory to conventional therapy, except for de novo AML. Full article
(This article belongs to the Special Issue Genomic Alterations in Leukemia (Volume II))
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