PDX1 DNA Methylation Distinguishes Two Subtypes of Pancreatic Neuroendocrine Neoplasms with a Different Prognosis
Abstract
:1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Exploratory DNA Methylation Analysis of EPIC Study Cohort
2.3. PDX1 Methylation Status Distinguishes A and B Subtype
2.4. Subtype Associates with Functionality and Metastatic Potential
2.5. Subtypes Have a Different Prognosis
2.6. Copy Number Alterations are Different between the Two Subtypes
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Tissue Procurement and Nucleotide Extraction
4.3. Mutation Analysis
4.4. DNA Methylation Analysis
4.5. Additional DNA Methylation Data
4.6. Exploratory DNA Methylation Data Analysis
4.7. PDX1 Data Analysis
4.8. Copy Number Alteration Calling
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Clinicopathological Parameter | Subtype A | Subtype B | p-Value |
---|---|---|---|
Gender | 0.20 | ||
F | 25 | 13 | |
M | 32 | 8 | |
Mutation MEN1/ATRX/DAXX | 7.6E-06 | ||
No | 10 | 13 | |
Yes | 38 | 2 | |
WHO Grade | 0.66 | ||
G1 | 27 | 12 | |
G2 | 22 | 8 | |
G3 | 3 | 0 | |
Functionality | 0.011 | ||
Gastrinoma | 1 | 1 | |
Glucagonoma | 1 | 0 | |
Insulinoma | 2 | 6 | |
Non-functional | 46 | 13 | |
VIPoma | 2 | 0 | |
LVI | 0.059 | ||
No | 14 | 8 | |
Yes | 31 | 5 | |
Distant metastasis | 0.022 | ||
No | 32 | 18 | |
Yes | 21 | 2 | |
Recurrence | 5.9E-04 | ||
No | 14 | 16 | |
Yes | 13 | 0 | |
Age | 57.1 (±12.1) | 53.1 (±15.0) | 0.29 |
Tumor size | 4.4 (±2.6) | 3.77 (±3.2) | 0.18 |
Patient | Gene | Mutation | Allelic Ratio WES | Sanger Validated? |
---|---|---|---|---|
UZA-01 | MEN1 | chr11:64572212 CG > C (frameshift) | 100% | Yes |
UZA-01 | MEN1 | chr11:64571924 G > T (stopgain) | 11% | No |
UZA-03 | DAXX | chr6:33288573 G > A (stopgain) | 60% | Yes |
UZA-06 | DAXX | chr6:33289250 G > A (missense) | 8% | No |
UZA-07 | MEN1 | chr11:64575561 C > A (missense) | 53% | Yes |
UZA-07 | DAXX | chr6:33287917 C > A (stopgain) | 48% | Yes |
UZA-08 | ATRX | chrX:76938655 T > C (missense) | 5% | No |
Lawrence-001 | MEN1 | chr11:64577293 T/TC (frameshift) | / | Yes |
Lawrence-002 | MEN1 | chr11:64575561 C/CA (frameshift) | / | Yes |
Lawrence-003 | MEN1 | chr11:64575530 C/T (missense) | / | Yes |
Lawrence-004 | MEN1 | chr11:64573723 TGTCCGCCCAGGC/T (in-frame deletion) | / | Yes |
Lawrence-004 | ATRX | chrX:76944420 TCTAGGAGAAAGGA/T (splicing) | / | Yes |
Lawrence-006 | MEN1 | chr11:64572613 G/GCAA (in-frame insertion) | / | Yes |
Lawrence-008 | MEN1 | chr11:64573744 CT/C (frameshift) | / | Yes |
Lawrence-009 | ATRX | chrX:76813035 C/A (stopgain) | / | Yes |
Lawrence-011 | MEN1 | chr11:64572078 63Nucleotides/G (frameshift) | / | No |
Lawrence-011 | DAXX | chr6:33287491 33Nucleotides/C (frameshift) | / | Yes |
Lawrence-012 | MEN1 | chr11:64577329 TAGAC/T (frameshift) | / | Yes |
Lawrence-012 | ATRX | chrX:76778831 CTACAAT/C (in-frame deletion) | / | Yes |
Lawrence-013 | MEN1 | chr11:64572643 G/A (stopgain) | / | Yes |
Lawrence-014 | MEN1 | chr11:64575550 C/A (missense) | / | Yes |
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Boons, G.; Vandamme, T.; Ibrahim, J.; Roeyen, G.; Driessen, A.; Peeters, D.; Lawrence, B.; Print, C.; Peeters, M.; Van Camp, G.; et al. PDX1 DNA Methylation Distinguishes Two Subtypes of Pancreatic Neuroendocrine Neoplasms with a Different Prognosis. Cancers 2020, 12, 1461. https://doi.org/10.3390/cancers12061461
Boons G, Vandamme T, Ibrahim J, Roeyen G, Driessen A, Peeters D, Lawrence B, Print C, Peeters M, Van Camp G, et al. PDX1 DNA Methylation Distinguishes Two Subtypes of Pancreatic Neuroendocrine Neoplasms with a Different Prognosis. Cancers. 2020; 12(6):1461. https://doi.org/10.3390/cancers12061461
Chicago/Turabian StyleBoons, Gitta, Timon Vandamme, Joe Ibrahim, Geert Roeyen, Ann Driessen, Dieter Peeters, Ben Lawrence, Cristin Print, Marc Peeters, Guy Van Camp, and et al. 2020. "PDX1 DNA Methylation Distinguishes Two Subtypes of Pancreatic Neuroendocrine Neoplasms with a Different Prognosis" Cancers 12, no. 6: 1461. https://doi.org/10.3390/cancers12061461