title: High prevalence of BRCA1 and BRCA2 germline mutations with loss of heterozygosity in a series of resected pancreatic adenocarcinoma and other neoplastic lesions.
abstract: OBJECTIVE
  Pancreatic ductal adenocarcinoma (PDAC) is associated with the breast ovarian cancer syndrome (BRCA1/BRCA2) mutations. It is unknown if this association is causal.
  
  
  METHODS
  This is a single-site study of patients who underwent surgical pancreatic tumor resection and self-identified as Ashkenazi Jewish. DNA from normal pancreatic tissue was genotyped for the three Ashkenazi Jewish BRCA1/2 founder mutations BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT, and loss of heterozygosity (LOH) was determined by sequencing DNA from microdissected tumor. When additional tumor tissue was available, p53 immunohistochemistry (IHC) was conducted.
  
  
  RESULTS
  Thirty-seven patients underwent surgery for PDAC, seven for intraductal papillary mucinous neoplasm (IPMN), and 19 for other diseases. A high prevalence of BRCA1/2 mutations was found in the surgical cohort (12/63; 19.0%; P < 0.001), PDAC cohort (8/37; 21.6%; P < 0.001), and IPMN cohort (2/7; 28.6%; P = .01) compared with published control mutation frequency. A high prevalence of BRCA1 185delAG (8.1%; P < 0.001) and BRCA2 6174delT (10.8%; P < 0.001) in Ashkenazi Jewish patients with PDAC was shown. BRCA1/2 LOH was found in 2 of 4 BRCA1-associated PDACs and 3 of 4 BRCA2-associated PDACs. Positive p53 IHC was found in 5 of 8 BRCA1/2 PDACs.
  
  
  CONCLUSIONS
  We show a high prevalence of BRCA1/2 mutations with LOH in an Ashkenazi Jewish cohort of surgically resected PDAC and neoplastic lesions, suggesting that these germline mutations are causal in selected individuals.
authors: Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. aimee.lucas@mssm.edu
authors: Aimee L
authors: AL
authors: Lucas
authors: Reena
authors: R
authors: Shakya
authors: Marla D
authors: MD
authors: Lipsyc
authors: Elana B
authors: EB
authors: Mitchel
authors: Sheila
authors: S
authors: Kumar
authors: Caroline
authors: C
authors: Hwang
authors: Liyong
authors: L
authors: Deng
authors: Catherine
authors: C
authors: Devoe
authors: John A
authors: JA
authors: Chabot
authors: Matthias
authors: M
authors: Szabolcs
authors: Thomas
authors: T
authors: Ludwig
authors: Wendy K
authors: WK
authors: Chung
authors: Harold
authors: H
authors: Frucht
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D007585:Jews / Q000235:genetics; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015995:Prevalence; D012307:Risk Factors
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