Dataset Information

High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer.

ABSTRACT: Introduction: We aimed to determine the prevalence and landscape of germline mutations among patients with young-onset pancreatic ductal adenocarcinoma (PDAC) as well as their influence in prognosis.Methods: Patients from two cohorts were studied, the high-risk cohort (HRC), which included 584 PDAC patients who received genetic counseling at The University of Texas MD Anderson Cancer Center, and a general cohort (GC) with 233 metastatic PDAC patients. We defined germline DNA sequencing on 13 known pancreatic cancer susceptibility genes. The prevalence and landscape of mutations were determined, and clinical characteristics including survival were analyzed.Results: A total of 409 patients underwent genetic testing (277 from HRC and 132 from GC). As expected, the HRC had higher prevalence of germline mutations compared with the GC: 17.3% versus 6.81%. The most common mutations in both cohorts were in BRCA1/2 and mismatch-repair (MMR) genes. Patients younger than 60 years old had significantly higher prevalence of germline mutations in both the HRC [odds ratios (OR), 1.93 ± 1.03-3.70, P = 0.039] and GC (4.78 ± 1.10-32.95, P = 0.036). Furthermore, PDAC patients with germline mutations in the GC had better overall survival than patients without mutations (HR, 0.44; 95% CI of HR, 0.25-0.76, P = 0.030).Discussion: Germline mutations are highly prevalent in patients with PDAC of early onset and can be predictive of better outcomes. Considering emerging screening strategies for relatives carrying susceptibility genes as well as impact on therapy choices, genetic counseling and testing should be encouraged in PDAC patients, particularly those of young onset. Cancer Prev Res; 11(11); 679-86. ©2018 AACR.

SUBMITTER: Bannon SA

PROVIDER: S-EPMC6343472 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer.

Bannon Sarah A SA Montiel Maria F MF Goldstein Jennifer B JB Dong Wenli W Mork Maureen E ME Borras Ester E Hasanov Merve M Varadhachary Gauri R GR Maitra Anirban A Katz Matthew H MH Feng Lei L Futreal Andrew A Fogelman David R DR Vilar Eduardo E McAllister Florencia F

Cancer prevention research (Philadelphia, Pa.) 20181001 11

<b>Introduction:</b> We aimed to determine the prevalence and landscape of germline mutations among patients with young-onset pancreatic ductal adenocarcinoma (PDAC) as well as their influence in prognosis.<b>Methods:</b> Patients from two cohorts were studied, the high-risk cohort (HRC), which included 584 PDAC patients who received genetic counseling at The University of Texas MD Anderson Cancer Center, and a general cohort (GC) with 233 metastatic PDAC patients. We defined germline DNA sequen ...[more]

PMID: 30274973

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Project description:BackgroundExosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC).Patients and methodsPatient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13. A cumulative series of 263 individuals were studied, including a discovery cohort of 142 individuals: 68 PDAC patients of all stages; 20 PDAC patients initially staged with localized disease, with blood drawn after resection for curative intent; and 54 age-matched healthy controls. A validation cohort of 121 individuals (39 cancer patients and 82 healthy controls) was studied to validate KRAS detection rates in early-stage PDAC patients. Primary outcome was circulating KRAS status as detected by droplet digital PCR. Secondary outcomes were disease-free and overall survival.ResultsKRAS mutations in exoDNA, were identified in 7.4%, 66.7%, 80%, and 85% of age-matched controls, localized, locally advanced, and metastatic PDAC patients, respectively. Comparatively, mutant KRAS cfDNA was detected in 14.8%, 45.5%, 30.8%, and 57.9% of these individuals. Higher exoKRAS MAFs were associated with decreased disease-free survival in patients with localized disease. In the validation cohort, mutant KRAS exoDNA was detected in 43.6% of early-stage PDAC patients and 20% of healthy controls.ConclusionsExosomes are a distinct source of tumor DNA that may be complementary to other liquid biopsy DNA sources. A higher percentage of patients with localized PDAC exhibited detectable KRAS mutations in exoDNA than previously reported for cfDNA. A substantial minority of healthy samples demonstrated mutant KRAS in circulation, dictating careful consideration and application of liquid biopsy findings, which may limit its utility as a broad cancer-screening method.

Dataset Information

High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer.

Publications

High Prevalence of Hereditary Cancer Syndromes and Outcomes in Adults with Early-Onset Pancreatic Cancer.

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