Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas

Scientific Reports
Toru FurukawaKeiko Shiratori

Abstract

Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we identified recurrent mutations of BRCA2 and FAT genes. BRCA2 showed somatic or germline premature termination mutations, with loss of the wild-type allele in 3 of 7 tumors. FAT1, FAT3, and FAT4 showed somatic or germline missense mutations in 4 of 7 tumors. The germline FAT mutations were with loss of the wild-type allele. Loss of BRCA2 expression was observed in 5 of 11 tumors. One patient with a BRCA2-mutated tumor experienced complete remission of liver metastasis following cisplatinum chemotherapy. In conclusion, acinar cell carcinomas show a distinct mutation pattern and often harbor somatic or germline mutations of BRCA2 and FAT genes. This result may warrant assessment of BRCA2 abrogation in patients with the carcinoma to determine thei...Continue Reading

References

Oct 26, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michiel S van der HeijdenScott E Kern
Oct 7, 2008·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·C Max SchmidtKarl Y Bilimoria
Sep 8, 2009·Genomics·Keiko ShimojimaToshiyuki Yamamoto
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
May 25, 2010·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Yuko KubokiToru Furukawa
Apr 5, 2011·American Journal of Human Genetics·Abel González-Pérez, Nuria López-Bigas
Aug 11, 2011·Bioinformatics·Jarupon Fah SathirapongsasutiStanley F Nelson
Dec 2, 2011·Neoplasia : an International Journal for Oncology Research·Robert J LonigroArul M Chinnaiyan
Oct 19, 2012·International Journal of Oncology·Masaru Katoh
Mar 30, 2013·Science·Bert VogelsteinKenneth W Kinzler
Dec 3, 2013·The Journal of Pathology·Yuchen JiaoLaura D Wood

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Citations

Feb 24, 2016·Biochemical and Biophysical Research Communications·Gerald S BraunMarcus J Moeller
Feb 13, 2016·Proceedings of the National Academy of Sciences of the United States of America·Mark BiBrian Shuch
Jan 17, 2016·Genes, Chromosomes & Cancer·Akito DobashiKengo Takeuchi
Sep 15, 2015·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Irene EspositoGünter Klöppel
Oct 4, 2016·Nature Reviews. Nephrology·Yasser Riazalhosseini, Mark Lathrop
Nov 20, 2016·Cancer Research and Treatment : Official Journal of Korean Cancer Association·Changhoon YooHeung-Moon Chang
Dec 21, 2017·World Journal of Gastroenterology : WJG·Ahmad Al-HaderDaniel Von Hoff
Oct 6, 2018·Cytopathology : Official Journal of the British Society for Clinical Cytology·Yorihiko TakaseJun Akiba
Apr 20, 2019·Cancer Biology & Therapy·Valentyna KryklyvaLodewijk A A Brosens
Aug 5, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Olca BasturkDavid S Klimstra
Sep 29, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Angela ChouAnthony J Gill
Dec 24, 2019·Archives of Pathology & Laboratory Medicine·Elizabeth D Thompson, Laura D Wood
Sep 9, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Lu WangDavid S Klimstra
May 3, 2020·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Owen W J PrallAnthony J Gill
Sep 4, 2020·World Journal of Gastrointestinal Oncology·Monica NigerMaria Di Bartolomeo
Oct 1, 2019·Computational and Mathematical Methods in Medicine·Xinxing GuoJing Chen
Nov 15, 2016·Cancer Control : Journal of the Moffitt Cancer Center·Evan S GlazerMokenge P Malafa
Jan 7, 2021·Journal of the National Comprehensive Cancer Network : JNCCN·Medhavi GuptaChristos Fountzilas
May 24, 2021·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Vishwajith SridharanYasmin G Hernandez-Barco
Jul 16, 2021·British Journal of Cancer·Eleonora LaiMario Scartozzi

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Methods Mentioned

BETA
Feature Extraction

Software Mentioned

Polyphen
Agilent Feature Extraction
Agilent Genomic Workbench
R
ExomeCNV
LifeScope
COSMIC
house
SOLiD

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