Whole-exome sequencing of duodenal neuroendocrine tumors in patients with neurofibromatosis type 1

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Michaël NoëLaura D Wood

Abstract

Neurofibromatosis type 1 (NF1) is a hereditary cancer predisposition syndrome characterized by frequent cutaneous and nervous system abnormalities. Patients with NF1 also have an increased prevalence of multiple gastrointestinal and peripancreatic neoplasms-neuroendocrine tumors of the ampulla that express somatostatin are particularly characteristic of NF1. In this study, we characterize the genetic alterations of a clinically well-characterized cohort of six NF1-associated duodenal neuroendocrine tumors using whole-exome sequencing. We identified inactivating somatic mutations in the NF1 gene in three of six tumors; the only other gene altered in more than one tumor was IFNB1. Copy number analysis revealed deletion/loss of heterozygosity of chromosome 22 in three of six patients. Analysis of germline variants revealed germline deleterious NF1 variants in four of six patients, as well as deleterious variants in other tumor suppressor genes in two of four patients with deleterious NF1 variants. Taken together, these data confirm the importance of somatic inactivation of the wild-type NF1 allele in the formation of NF1-associated duodenal neuroendocrine tumors and suggest that loss of chromosome 22 is important in at least a sub...Continue Reading

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Citations

Jan 19, 2019·Endocrine Reviews·Andrea Mafficini, Aldo Scarpa
Jul 2, 2019·The American Journal of Surgical Pathology·Michaël NoëLodewijk A A Brosens
Nov 30, 2018·World Journal of Gastrointestinal Oncology·Antonio PeaClaudio Luchini
Mar 10, 2021·Pathologica·Massimo MilioneAlessandro Vanoli

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Methods Mentioned

BETA
Fluorescence

Software Mentioned

Varscan
VariantDx
CNVkit
ASCAT

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