Supplementary Table 1. Reported Index Cases with a Confirmed Constitutional MLH1 Epimutation

Supplementary Information

Supplementary Table 1. Reported index cases with a confirmed constitutional MLH1 epimutation.

Clinical, tumour and molecular features are summarized for cases with a constitutional MLH1 epimutation in the chronological order in which they were identified. Cases in parentheses are considered herein as probable carriers of an MLH1 epimutation, but are currently unconfirmed based on the information published. Green font is used to highlight one familial case where non-Mendelian intergenerational transmission of the epimutation was proven. Blue font highlights familial cases where the epimutation has been linked to a genetic defect on the epimutated allele and/or autosomal dominant inheritance of the epimutation has been demonstrated by linkage to or segregation with, a particular genetic allele between generations. † Personal communication with the authors. M, male; F, female; y, years; Asc, ascending; Desc, descending; Sig, sigmoid; Trans, transverse; Hep flex, hepatic flexure; Sync, synchronous; Am, Amsterdam criteria; BG, Bethesda guidelines; Mod, modified; Rev, Revised; C; criterion within specified clinical guidelines, MSI, microsatellite unstable; MSS, microsatellite stable; IHC, immunohistochemistry; LOH, loss of heterozygosity; ROH, retention of heterozygosity; WT, wild-type; KRAS+, positive for KRAS hot-spot mutation within codon 12 or 13; CIMP+, positive for CpG island methylator phenotype; HP, hyperplastic polyp; FH, family history; FDRs, first degree relatives; MSP, methylation-specific PCR; NA, not available for study. Analyses of tumours for MLH1 expression and the nature of the second hit were not assessed in some cases due to the lack of available specimen. The mean age of onset of the first colorectal cancer in the confirmed cases (excluding those in parentheses) is 39.2 ±11.1 years and for all cases listed is 40.1 ±10.7 years.

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