Germline whole-exome sequencing of patients with neuroendocrine neoplasms reveals pathogenic or likely pathogenic variants in a large subset of patients

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Introduction: The germline predisposition to neuroendocrine neoplasms (NEN) is not-well understood beyond genetic syndromes associated with MEN1 loss.

Aim(s): We conducted whole-exome sequencing (WES) of germline DNA from a prospective cohort of patients with NENs (n=151) treated at the Ohio State University to better understand the genetic predisposition to NENs.

Materials and methods: Variants obtained from WES were filtered using the following criteria: Minimum read coverage of 20 with at least 3 altered reads, minimum variant allele frequency of 15%, quality score >100. Long INDELs with length >= 10 were eliminated. Variant Effect Predictor (Release 107) was applied for functional prediction and to obtain population allele frequencies. Variants were refined to have population minor allele frequencies (MAF) < 0.01 in several databases. Variants were restricted to those among 974 genes obtained by combining publicly available gene lists (Invitae, GeneDx, Tlemsani et. al.). Fisher’s exact tests were used to compare the frequencies of pathogenic/likely pathogenic germline variants with a reference population (n=74,023) from gnomad V3.1 non-Cancer.

Conference:

Presenting Author: Sukrithan V

Authors: Sukrithan V, Boateng I, Jain P, Liyanarachchi S, Buss J,

Keywords: whole exome sequencing, germline, population, mutyh, pkd1, atp4a, pah,