Dataset Information

Germline alterations in patients with biliary tract cancers: A spectrum of significant and previously underappreciated findings.

ABSTRACT:

Background

With limited information on germline mutations in biliary tract cancers, this study performed somatic and germline testing for patients at Memorial Sloan Kettering Cancer Center with known biliary tract carcinoma with the aim of determining the frequency and range of pathogenic germline alterations (PGAs).

Methods

Patients with biliary tract carcinoma were consented for somatic tumor and matched blood testing of up to 468 genes via the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets next-generation sequencing platform. A germline variant analysis was performed on a panel of up to 88 genes associated with an increased predisposition for cancer. Demographic and diagnostic details were collected.

Results

Germline mutations were tested in 131 patients. Intrahepatic cholangiocarcinoma was the most common cancer (63.4%), and it was followed by gallbladder adenocarcinoma (16.8%), extrahepatic cholangiocarcinoma (16%), and otherwise unspecified biliary tract cancer (3.8%). Known and likely PGAs were present in 21 patients (16.0%), with 9.9% harboring a PGA in a high/moderate-penetrance cancer predisposition gene. Among high-penetrance cancer susceptibility genes, PGAs were most commonly observed in BRCA1 and BRCA2 (33.3%), which made up 5.3% of the entire cohort, and they were followed by PALB2, BAP1, and PMS2. Mutations in ATM, MITF, and NBN, moderate-penetrance cancer susceptibility genes, were identified in 1 patient each. There was no observed difference in the types of mutations among the subtypes of biliary tract cancer.

Conclusions

The frequency of PGAs found was comparable to existing data on the prevalence of germline mutations in other solid tumor types with matched tumor analysis. This provides support for the role of the BRCA1/2, ATM, and BAP1 genes in biliary tract cancer susceptibility.

SUBMITTER: Maynard H

PROVIDER: S-EPMC7584349 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Germline alterations in patients with biliary tract cancers: A spectrum of significant and previously underappreciated findings.

Maynard Hannah H Stadler Zsofia K ZK Berger Michael F MF Solit David B DB Ly Michele M Lowery Maeve A MA Mandelker Diana D Zhang Liying L Jordan Emmett E El Dika Imane I Kemel Yelena Y Ladanyi Marc M Robson Mark E ME O'Reilly Eileen M EM Abou-Alfa Ghassan K GK

Cancer 20200101 9

<h4>Background</h4>With limited information on germline mutations in biliary tract cancers, this study performed somatic and germline testing for patients at Memorial Sloan Kettering Cancer Center with known biliary tract carcinoma with the aim of determining the frequency and range of pathogenic germline alterations (PGAs).<h4>Methods</h4>Patients with biliary tract carcinoma were consented for somatic tumor and matched blood testing of up to 468 genes via the Memorial Sloan Kettering Cancer Ce ...[more]

PMID: 32012241

Similar Datasets

Project description:Background & aimsGallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.MethodsWe pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.ResultsDuring 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.ConclusionWe observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.Lay summaryOur findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

Dataset Information

Germline alterations in patients with biliary tract cancers: A spectrum of significant and previously underappreciated findings.

Background

Methods

Results

Conclusions

Publications

Germline alterations in patients with biliary tract cancers: A spectrum of significant and previously underappreciated findings.

Similar Datasets

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