Compound Heterozygous Variants in Pediatric Cancers: A Systematic Review

Frontiers in Genetics
Dustin B Miller, Stephen R Piccolo

Abstract

A compound heterozygous (CH) variant is a type of germline variant that occurs when each parent donates one alternate allele and these alleles are located at different loci within the same gene. Pathogenic germline variants have been identified for some pediatric cancer types but in most studies, CH variants are overlooked. Thus, the prevalence of pathogenic CH variants in most pediatric cancer types is unknown. We identified 26 studies (published between 1999 and 2019) that identified a CH variant in at least one pediatric cancer patient. These studies encompass 21 cancer types and have collectively identified 25 different genes in which a CH variant occurred. However, the sequencing methods used and the number of patients and genes evaluated in each study were highly variable across the studies. In addition, methods for assessing pathogenicity of CH variants varied widely and were often not reported. In this review, we discuss technologies and methods for identifying CH variants, provide an overview of studies that have identified CH variants in pediatric cancer patients, provide insights into future directions in the field, and give a summary of publicly available pediatric cancer sequencing data. Although considerable insig...Continue Reading

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Citations

Mar 10, 2021·F1000Research·Dustin B Miller, Stephen R Piccolo
Apr 9, 2021·Frontiers in Genetics·Dustin B Miller, Stephen R Piccolo
Oct 9, 2021·PloS One·Dustin B MillerStephen R Piccolo
Sep 26, 2021·Cancer Research·Troy A McEachron, Lee J Helman

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Methods Mentioned

BETA
RNA-seq
exome sequencing

Software Mentioned

ClinVar Predictor
Google Scholar
ClinVar
PolyPhen
TARGET
COSMIC
SIFT

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