Exome sequencing in 51 early onset non-familial CRC cases

Molecular Genetics & Genomic Medicine
Jessada ThutkawkorapinEmma Tham

Abstract

Colorectal cancer (CRC) cases with an age of onset <40 years suggests a germline genetic cause. In total, 51 simplex cases were included to test the hypothesis of CRC as a mendelian trait caused by either heterozygous autosomal dominant or bi-allelic autosomal recessive pathogenic variants. The cohort was whole exome sequenced (WES) at 100× coverage. Both a dominant- and recessive model were used for searching predisposing genetic factors. In addition, we assayed recessive variants of potential moderate risk that were enriched in our young-onset CRC cohort. Variants were filtered using a candidate cancer gene list or by selecting variants more likely to be pathogenic based on variant type (e.g., loss-of-function) or allele frequency. We identified one pathogenic variant in PTEN in a patient subsequently confirmed to have a hereditary hamartoma tumor syndrome (Cowden syndrome) and one patient with a pathogenic heterozygous variant in PMS2 that was originally not identified by WES due to low quality reads resulting from pseudogenes. In addition, we identified three heterozygous candidate missense variants in known cancer susceptibility genes (BMPR1A, BRIP1, and SRC), three truncating variants in possibly novel cancer genes (CLSPN...Continue Reading

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Citations

Apr 23, 2020·Molecular Biology of the Cell·Andrew C TamashunasTanmay P Lele
Oct 28, 2020·Chemistry : a European Journal·Yukishige ItoYoichi Takeda
Nov 25, 2020·International Journal of Molecular Sciences·Iris B A W Te PaskeRicharda M de Voer
Oct 30, 2020·Cancer Prevention Research·Lorena Martín-MoralesTrinidad Caldés
Aug 31, 2021·World Journal of Gastrointestinal Oncology·Joy Zhou Done, Sandy H Fang

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Methods Mentioned

BETA
exome sequencing
PCR
chip
genotyping
xenografts

Software Mentioned

ExAC
gnomAD
Phylop
GERP + +
LRT
cBioportal
Mutation Assessor
PolyPhen2 HVAR
Mutation Taster
PolyPhen2 HDIV

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