Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history.

Published on Jan 1, 2018in Genetics in Medicine8.904
· DOI :10.1038/GIM.2017.85
Kari G. Chaffee23
Estimated H-index: 23
(Mayo Clinic),
Ann L. Oberg69
Estimated H-index: 69
(Mayo Clinic)
+ 7 AuthorsGloria M. Petersen121
Estimated H-index: 121
(Mayo Clinic)
Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history
Figures & Tables
📖 Papers frequently viewed together
165 Citations
15 Authors (Marcia I. Canto, ..., Marco J. Bruno)
477 Citations
337 Citations
#1Eric RosenthalH-Index: 7
#1Cedric Van Marcke (Cliniques Universitaires Saint-Luc)H-Index: 3
Last. Susan ManleyH-Index: 7
view all 7 authors...
Abstract Purpose Breast MRI screening is recommended for women with a >20% lifetime risk for breast cancer on the basis of estimates derived from risk models dependent largely on family history. Alternatively, a >20% lifetime risk can be established through genetic testing of BRCA1 and BRCA2 , as well as a growing selection of other genes associated with inherited breast cancer risk. The aim of this study was to quantify the impact of testing for genes other than BRCA1/2 and the extent to which ...
13 CitationsSource
#1Nadine Tung (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 76
#2Nan Lin (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 109
Last. Judy Garber (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 168
view all 9 authors...
PurposeTesting for germline mutations in BRCA1/2 is standard for select patients with breast cancer to guide clinical management. Next-generation sequencing (NGS) allows testing for mutations in additional breast cancer predisposition genes. The frequency of germline mutations detected by using NGS has been reported in patients with breast cancer who were referred for BRCA1/2 testing or with triple-negative breast cancer. We assessed the frequency and predictors of mutations in 25 cancer predisp...
241 CitationsSource
#1Dawn Provenzale (Duke University)H-Index: 56
#2Samir Gupta (UCSD: University of California, San Diego)H-Index: 43
Last. Susan Darlow (Duke University)H-Index: 1
view all 29 authors...
Abstract This is a focused update highlighting the most current NCCN Guidelines for diagnosis and management of Lynch syndrome. Lynch syndrome is the most common cause of hereditary colorectal cancer, usually resulting from a germline mutation in 1 of 4 DNA mismatch repair genes (MLH1, MSH2, MSH6, or PMS2), or deletions in the EPCAM promoter. Patients with Lynch syndrome are at an increased lifetime risk, compared with the general population, for colorectal cancer, endometrial cancer, and other ...
125 CitationsSource
#1Xiaohong R. Yang (NIH: National Institutes of Health)H-Index: 27
#2Melissa Rotunno (NIH: National Institutes of Health)H-Index: 21
Last. Alisa M. Goldstein (NIH: National Institutes of Health)H-Index: 86
view all 32 authors...
The risk of pancreatic cancer (PC) is increased in melanoma-prone families but the causal relationship between germline CDKN2A mutations and PC risk is uncertain, suggesting the existence of non-CDKN2A factors. One genetic possibility involves patients having mutations in multiple high-risk PC-related genes; however, no systematic examination has yet been conducted. We used next-generation sequencing data to examine 24 putative PC-related genes in 43 PC patients with and 23 PC patients without g...
16 CitationsSource
#1Nicholas J. Roberts (Johns Hopkins University)H-Index: 20
#2Alexis L. Norris (Johns Hopkins University)H-Index: 10
Last. Alison P. Klein (Johns Hopkins University)H-Index: 67
view all 45 authors...
Pancreatic cancer is projected to become the second leading cause of cancer-related death in the United States by 2020. A familial aggregation of pancreatic cancer has been established, but the cause of this aggregation in most families is unknown. To determine the genetic basis of susceptibility in these families, we sequenced the germline genome of 638 familial pancreatic cancer patients. We also sequenced the exomes of 39 familial pancreatic adenocarcinomas. Our analyses support the role of p...
175 CitationsSource
#1Alyssa L. Smith (McGill University)H-Index: 7
#2Najmeh Alirezaie (McGill University)H-Index: 9
Last. George Zogopoulos (McGill University)H-Index: 23
view all 22 authors...
The genetic basis underlying the majority of hereditary pancreatic adenocarcinoma (PC) is unknown. Since DNA repair genes are widely implicated in gastrointestinal malignancies, including PC, we hypothesized that there are novel DNA repair PC susceptibility genes. As germline DNA repair gene mutations may lead to PC subtypes with selective therapeutic responses, we also hypothesized that there is an overall survival (OS) difference in mutation carriers versus non-carriers. We therefore interroga...
34 CitationsSource
#1Chunling Hu (Mayo Clinic)H-Index: 25
#1Chunling Hu (Mayo Clinic)H-Index: 10
Last. Fergus J. Couch (Mayo Clinic)H-Index: 115
view all 10 authors...
The prevalence of germline pathogenic mutations in a comprehensive panel of cancer predisposition genes is not well defined for patients with pancreatic ductal adenocarcinoma (PDAC). To estimate the frequency of mutations in a panel of 22 cancer predisposition genes, 96 patients unselected for a family history of cancer who were recruited to the Mayo Clinic Pancreatic Cancer patient registry over a 12 month period were screened by next-generation sequencing. Fourteen pathogenic mutations in 13 p...
81 CitationsSource
#1Matthew B. Yurgelun (Harvard University)H-Index: 23
#2Brian C. AllenH-Index: 22
Last. Sapna SyngalH-Index: 75
view all 10 authors...
Background & Aims Multigene panels are commercially available tools for hereditary cancer risk assessment that allow for next-generation sequencing of numerous genes in parallel. However, it is not clear if these panels offer advantages over traditional genetic testing. We investigated the number of cancer predisposition gene mutations identified by parallel sequencing in individuals with suspected Lynch syndrome. Methods We performed germline analysis with a 25-gene, next-generation sequencing ...
165 CitationsSource
Familial pancreatic cancer (FPC) designates kindreds that contain at least two first degree relatives with pancreatic ductal adenocarcinoma. Studies of FPC have focused on discovery of genetic etiology and on management of those at genetically high risk. Over a decade of research reveals that a half dozen known hereditary syndromes or genes are associated with increased risk of developing pancreatic cancer, the most prominent of which are BRCA2 and CDKN2A. The search for novel predisposition gen...
30 CitationsSource
#1David B. Zhen (Mayo Clinic)H-Index: 3
#2Kari G. Rabe (Mayo Clinic)H-Index: 39
Last. Gloria M. Petersen (Mayo Clinic)H-Index: 121
view all 18 authors...
BRCA1 , BRCA2 , PALB2 , and CDKN2A mutations in familial pancreatic cancer: a PACGENE study
146 CitationsSource
Cited By55
#1Fionnuala Crowley (Mount Sinai Hospital)
#2Wungki ParkH-Index: 14
Last. Eileen M. O'Reilly (Cornell University)H-Index: 73
view all 3 authors...
Pancreas ductal adenocarcinoma (PDAC) is the third most common cause of cancer death in the USA. While other cancers with historically poor prognoses have benefited from new immunotherapies and targeted agents, the 5-year survival rate for PDAC patients has remained static. The accessibility to genomic testing has improved in recent years, and it is now clear that PDAC is a heterogenous disease, with a subset of patients harboring actionable mutations. There are several targeted therapies approv...
1 CitationsSource
#2Tanya Dwarte (Garvan Institute of Medical Research)H-Index: 1
Last. Amber L. Johns (Garvan Institute of Medical Research)H-Index: 27
view all 0 authors...
Background null The Australian Pancreatic Cancer Screening Program (APCSP) offers endoscopic ultrasound surveillance for individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) with all participants requiring assessment by a Familial Cancer Service before or after study enrolment. null Methods null Individuals aged 40-80 years (or 10 years younger than the earliest PDAC diagnosis) were eligible for APCSP study entry if they had 1) ≥ two blood relatives with PDAC (at least one of...
#1Kung-Kai Kuo (KMU: Kaohsiung Medical University)H-Index: 20
#2Pi-Jung Hsiao (ISU: I-Shou University)H-Index: 1
Last. Kohsuke Kato (University of Tsukuba)H-Index: 9
view all 13 authors...
The high mortality of pancreatic cancer is attributed to the insidious progression of this disease, which results in a delayed diagnosis and advanced disease stage at diagnosis. More than 35% of patients with pancreatic cancer are in stage III, whereas 50% are in stage IV at diagnosis. Thus, understanding the aggressive features of pancreatic cancer will contribute to the resolution of problems, such as its early recurrence, metastasis, and resistance to chemotherapy and radiotherapy. Therefore,...
#1Ming Tan (OUH: Odense University Hospital)H-Index: 2
#2Klaus Brusgaard (University of Southern Denmark)H-Index: 27
Last. Maiken Thyregod Joergensen (OUH: Odense University Hospital)H-Index: 10
view all 7 authors...
First-degree relatives (FDRs) of familial pancreatic cancer (FPC) patients have increased risk of developing pancreatic ductal adenocarcinoma (PDAC). Investigating and understanding the genetic basis for PDAC susceptibility in FPC predisposed families may contribute toward future risk-assessment and management of high-risk individuals. Using a Danish cohort of 27 FPC families, we performed whole-genome sequencing of 61 FDRs of FPC patients focusing on rare genetic variants that may contribute to...
#1Marco Bono (University of Palermo)H-Index: 5
#2Daniele Fanale (University of Palermo)H-Index: 22
Last. Chiara Brando (University of Palermo)H-Index: 3
view all 19 authors...
Background null Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes. null null null Patients and methods null Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing...
#1Samer Alkassis (WSU: Wayne State University)H-Index: 1
#2Omid Yazdanpanah (WSU: Wayne State University)H-Index: 1
Last. Philip A. PhilipH-Index: 76
view all 3 authors...
Introduction: Genomic instability resulting from DNA damage repair (DDR) deficiencies is a hallmark of cancer and offers treatment opportunities. Homologous recombination DDR defect is a result of multiple critical gene mutations, including BRCA1/2. Targeting DNA DDR defects in pancreatic cancer (PC) is emerging as a potential treatment strategy with current focus on BRCA mutations.Areas covered: Challenges in treating patients with PC are explained. We review DDR defects as a treatment target i...
#1Jian-Xiong Hu (Putian University)
#2Chengfei Zhao (Putian University)H-Index: 6
Last. Feng Gao (Fujian Medical University)H-Index: 9
view all 7 authors...
Despite rapid advances in modern medical technology and significant improvements in survival rates of many cancers, pancreatic cancer is still a highly lethal gastrointestinal cancer with a low 5-year survival rate and difficulty in early detection. At present, the incidence and mortality of pancreatic cancer are increasing year by year worldwide, no matter in the United States, Europe, Japan, or China. Globally, the incidence of pancreatic cancer is projected to increase to 18.6 per 100000 in 2...
#1Esteban Astiazaran-Symonds (NIH: National Institutes of Health)H-Index: 1
#2Alisa M. Goldstein (NIH: National Institutes of Health)H-Index: 86
The genetics of pancreatic ductal adenocarcinoma (PDAC) is complex with patients reported to harbor germline pathogenic variants (PVs) in many different genes. PDAC patients with familial pancreatic cancer (FPC) are more likely to carry germline PVs but there is no consensus main gene involved in FPC. We performed a systematic review of publications from PubMed and Scopus reporting PVs in patients with FPC, sporadic pancreatic cancer (SPC) and unselected cohorts of PDAC patients undergoing genet...
#1Ming Tan (OUH: Odense University Hospital)H-Index: 2
#2Klaus Brusgaard (University of Southern Denmark)H-Index: 27
Last. Maiken Thyregod Joergensen (OUH: Odense University Hospital)H-Index: 10
view all 7 authors...
Background null Familial Pancreatic Cancer (FPC) is responsible for up to 10% of all cases of pancreatic ductal adenocarcinoma (PDAC). Individuals predisposed for FPC have an estimated lifetime risk of 16-39% of developing PDAC. While heritability of PDAC has been estimated to be 36% in a Nordic twin study, no heritability estimate specific on FPC has been reported. null Methods null A national cohort of Danish families with predisposition for FPC is currently included in a screening program for...
1 CitationsSource
#1Fabienne Lesueur (Curie Institute)H-Index: 34
#2Douglas F. Easton (University of Cambridge)H-Index: 172
Last. Alejandro Moles-Fernández (University of Texas MD Anderson Cancer Center)
view all 1 authors...
The first International Workshop of the ATM and Cancer Risk group focusing on the role of Ataxia-Telangiectasia Mutated (ATM) gene in cancer was held on December 4 and 5, 2019 at Institut Curie in Paris, France. It was motivated by the fact that germline ATM pathogenic variants have been found to be associated with different cancer types. However, due to the lack of precise age-, sex-, and site-specific risk estimates, no consensus on management guidelines for variant carriers exists, and the cl...