Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms

Michael Skaro, Neha Nanda, Christian Gauthier, Matthäus Felsenstein, Zhengdong Jiang, Miaozhen Qiu, Koji Shindo, Jun Yu, Danielle Hutchings, Ammar A. Javed, Ross Beckman, Jin He, Christopher Wolfgang, Elizabeth Thompson, Ralph H Hruban, Alison Klein, Michael S Goggins, Laura Delong Wood, Nicholas Roberts

Research output: Contribution to journalArticle

Abstract

Background & Aims: Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. Methods: We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. Results: We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9–10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4–5.4). More patients with IPMNs carried germline mutations in ATM (P <.0001), PTCH1 (P <.0001), and SUFU (P <.0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P <.0320). Conclusions: In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

Original languageEnglish (US)
Pages (from-to)1905-1913
Number of pages9
JournalGastroenterology
Volume156
Issue number6
DOIs
StatePublished - May 1 2019

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Germ-Line Mutation
Neoplasms
Pancreatic Neoplasms
Mutation
Confidence Intervals
Exome

Keywords

  • Cancer
  • Genetics
  • Pancreas
  • Predisposition

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms. / Skaro, Michael; Nanda, Neha; Gauthier, Christian; Felsenstein, Matthäus; Jiang, Zhengdong; Qiu, Miaozhen; Shindo, Koji; Yu, Jun; Hutchings, Danielle; Javed, Ammar A.; Beckman, Ross; He, Jin; Wolfgang, Christopher; Thompson, Elizabeth; Hruban, Ralph H; Klein, Alison; Goggins, Michael S; Wood, Laura Delong; Roberts, Nicholas.

In: Gastroenterology, Vol. 156, No. 6, 01.05.2019, p. 1905-1913.

Research output: Contribution to journalArticle

Skaro, Michael ; Nanda, Neha ; Gauthier, Christian ; Felsenstein, Matthäus ; Jiang, Zhengdong ; Qiu, Miaozhen ; Shindo, Koji ; Yu, Jun ; Hutchings, Danielle ; Javed, Ammar A. ; Beckman, Ross ; He, Jin ; Wolfgang, Christopher ; Thompson, Elizabeth ; Hruban, Ralph H ; Klein, Alison ; Goggins, Michael S ; Wood, Laura Delong ; Roberts, Nicholas. / Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms. In: Gastroenterology. 2019 ; Vol. 156, No. 6. pp. 1905-1913.
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abstract = "Background & Aims: Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. Methods: We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. Results: We identified 23 patients with a germline mutation associated with cancer risk (7.3{\%}; 95{\%} confidence interval, 4.9–10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9{\%}; 95{\%} confidence interval, 1.4–5.4). More patients with IPMNs carried germline mutations in ATM (P <.0001), PTCH1 (P <.0001), and SUFU (P <.0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P <.0320). Conclusions: In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3{\%} to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.",
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T1 - Prevalence of Germline Mutations Associated With Cancer Risk in Patients With Intraductal Papillary Mucinous Neoplasms

AU - Skaro, Michael

AU - Nanda, Neha

AU - Gauthier, Christian

AU - Felsenstein, Matthäus

AU - Jiang, Zhengdong

AU - Qiu, Miaozhen

AU - Shindo, Koji

AU - Yu, Jun

AU - Hutchings, Danielle

AU - Javed, Ammar A.

AU - Beckman, Ross

AU - He, Jin

AU - Wolfgang, Christopher

AU - Thompson, Elizabeth

AU - Hruban, Ralph H

AU - Klein, Alison

AU - Goggins, Michael S

AU - Wood, Laura Delong

AU - Roberts, Nicholas

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Background & Aims: Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. Methods: We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. Results: We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9–10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4–5.4). More patients with IPMNs carried germline mutations in ATM (P <.0001), PTCH1 (P <.0001), and SUFU (P <.0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P <.0320). Conclusions: In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

AB - Background & Aims: Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. Methods: We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. Results: We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9–10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4–5.4). More patients with IPMNs carried germline mutations in ATM (P <.0001), PTCH1 (P <.0001), and SUFU (P <.0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P <.0320). Conclusions: In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer.

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KW - Genetics

KW - Pancreas

KW - Predisposition

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