Origin of Subsequent Malignant Neoplasms in Patients with History of Testicular Germ Cell Tumor
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Detection of i(12p) and Gain of 12p in SMNs
2.2. Evaluation of Genetic Concordance in the Somatic Transformation of TGCTs by Targeted DNA Sequencing
2.3. Evaluation of Differentially Expressed Genes in Matched Teratoma and Somatically Transformed Specimens by RNAseq
2.4. Growth of Teratoma Cell Cultures and Xenograft
2.5. Stemness Biomarker Expression
3. Discussion
4. Materials and Methods
4.1. Patient Identification
4.2. Fluorescent in Situ Hybridization (FISH)
4.3. DNA and RNA Sequencing
4.4. Primary Culture, Flow Cytometry, and Xenograft
4.5. DNA Sequencing Analysis
4.6. RNA Sequencing Analysis
4.7. Concordance of Mutations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Second Malignancy | Number of Cases |
---|---|
Total | 43 |
Gastrointestinal | 9 |
Colorectal | 6 |
Pancreas | 2 |
Adenocarcinoma | 1 |
Neuroendocrine | 1 |
Esophageal | 1 |
Lung | 7 |
Squamous | 3 |
Adenocarcinoma | 3 |
Neuroendocrine | 1 |
Genitourinary | 15 |
Renal cell | 8 |
Clear cell | 7 |
Papillary | 1 |
Urothelial | 5 |
Bladder | 4 |
Upper tract | 1 |
Prostate | 2 |
Sarcoma | 7 |
Leiomyosarcoma | 4 |
Retroperitoneal | 3 |
Gluteal | 1 |
Rhabdomyosarcoma | 1 |
Angiosarcoma | 1 |
Unclassified | 1 |
Melanoma | 3 |
Glioblastoma multiforme | 1 |
Adrenal cortical carcinoma | 1 |
Case No. | Primary Testicular Tumor | Age at Initial Diagnosis | Primary Treatment | Age at SMN | Time to SMN (Yrs.) | SMN Histology | Metastatic Tumor | % i(12p) FISH Positive | # i(12p) Copies |
1 | Seminoma * | 51 | BEP | 57 | 6.5 | Unclassified sarcoma | RP | 56% | 1–2 |
2 | Seminoma | 31 | XRT | 54 | 22.0 | Colorectal | Liver | 68% | 1 |
3 | Seminoma | 28 | XRT, BEP, HDC + SCT | 34 | 5.9 | LMS | Gluteus | 64% | 1–2 |
4 | Seminoma | 53 | BEP | 56 | 3.1 | Urothelial | Bladder | 39% | 1 |
5 | Nonseminoma | 39 | BEP | 39 | 0.4 | Pancreatic | Pancreas | 63% | 1–3 |
Case No. | Primary Histology | Age at Initial Diagnosis | Primary Treatment | Age at SMN | Time to SMN (Yrs.) | SMN Histology | Site of SMN | % Extra Copies Chromosome 12 | # i(12p) Copies |
6 | Seminoma | 33 | XRT | 51 | 18.0 | LMS | RP | 73% | 0 |
7 | Seminoma | 51 | XRT | 59 | 7.6 | Rectal (adenocarcinoma) | Rectum | 55% | 0 |
8 | Seminoma | 58 | XRT | 71 | 13.3 | Colorectal | Cecum | 36% | 0 |
9 | Seminoma | 57 | XRT | 65 | 8.5 | Lung (adenocarcinoma) | Lung | 72% | 0 |
10 | Seminoma | 29 | XRT | 59 | 24.6 | Melanoma | Axillary lymph node | 83% | 0 |
Nonseminoma | 44 | BEP | |||||||
11 | Seminoma | 22 | XRT | 58 | 9.6 | LMS | RP | 72% | 0 |
12 | Nonseminoma | 28 | CISCA/VB | 45 | 36.3 | LMS | RP | 74% | 0 |
13 | Seminoma | 53 | XRT | 58 | 44.8 | Colorectal | Lung | 83% | 0 |
14 | Seminoma | 62 | 65 | 5.2 | Lung (squamous) | Lung | 61% | 0 | |
15 | Seminoma | 27 | XRT | 81 | 3.0 | Urothelial | Bladder | 66% | 0 |
16 | NA | 20 | XRT + VB | 57 | 53.6 | Adrenal Cortical Carcinoma | Adrenal | 89% | 0 |
17 | Seminoma | 31 | XRT | 61 | 36.6 | Bladder | Bladder | 82% | 0 |
18 | Seminoma | 29 | CTX/carboplatin | 49 | 29.9 | Urothelial | Renal pelvis | 51% | 0 |
19 | Seminoma | 47 | XRT | 65 | 20.3 | Renal cell carcinoma | Kidney | 57% | 0 |
20 | Seminoma | 29 | PVB | 54 | 19.4 | Urothelial | Bladder | 91% | 0 |
CSC Surface Marker | Function | Adult Stem Cell Expression | Normal Tissue Expression | CSC Expression | % Cells Positive in Cell Line tera13 | % Cells Positive in Cell Line tera22 |
---|---|---|---|---|---|---|
SSEA3 | hESC marker | Mesenchymal | Rare | Embryonal, Breast | <1% | <1% |
SSEA4 | hESC marker | Mesenchymal, Cardiac, Gonad | Rare | Embryonal, Breast | 55% | 55% |
SSEA5 | hESC marker | NA | Unknown | Embryonal, Pancreatic, Colorectal, Urothelial | <1% | <1% |
TRA-1-60 | hESC marker | NA | Rare | Embryonal, Breast, Prostate | -- | -- |
TRA-1-81 | hESC marker | NA | Rare | Embryonal, Breast | -- | -- |
CD133 | Marker of hematopoietic stem cell | Hematopoietic, Prostate, Neural | Rare | Many * | 5% | <1% |
CD90 | Cell adhesion | Mesenchymal, Cardiac | Rare | Brain, Liver | >99% | >99% |
CD326 | Cell adhesion | No | Rare | Colon, Pancreas, Liver | -- | -- |
Cripto-1 (TDGF1) | Self-renewal | NA | Rare | Breast, Colon, Lung | 4% | 5% |
CD24 | B cell proliferation | Intestinal | Rare | Breast, Gastric, Pancreas | 25% | 2% |
CD117 (c-kit) | Receptor for stem cell factor | Mesenchymal, Cardiac | Rare | Ovary | 2% | -- |
CD26 | Dipeptidyl peptidase iv | Hematopoietic | Rare | Colorectal, Leukemia | 80% | >99% |
CD34 | Cell adhesion | Hematopoietic | Rare | Leukemia, SCC | 3% | 2% |
CD44 | Hyaluronic acid receptor | Hematopoietic, Adipose | Rare | Many ** | >99% | >99% |
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Umbreit, E.C.; Siddiqui, B.A.; Hwang, M.J.; Joon, A.Y.; Maity, T.; Westerman, M.E.; Merriman, K.W.; Alhasson, H.; Uthup, J.; Guo, T.; et al. Origin of Subsequent Malignant Neoplasms in Patients with History of Testicular Germ Cell Tumor. Cancers 2020, 12, 3755. https://doi.org/10.3390/cancers12123755
Umbreit EC, Siddiqui BA, Hwang MJ, Joon AY, Maity T, Westerman ME, Merriman KW, Alhasson H, Uthup J, Guo T, et al. Origin of Subsequent Malignant Neoplasms in Patients with History of Testicular Germ Cell Tumor. Cancers. 2020; 12(12):3755. https://doi.org/10.3390/cancers12123755
Chicago/Turabian StyleUmbreit, Eric C., Bilal A. Siddiqui, Michael J. Hwang, Aron Y. Joon, Tapati Maity, Mary E. Westerman, Kelly W. Merriman, Hussam Alhasson, Joma Uthup, Tao Guo, and et al. 2020. "Origin of Subsequent Malignant Neoplasms in Patients with History of Testicular Germ Cell Tumor" Cancers 12, no. 12: 3755. https://doi.org/10.3390/cancers12123755