Variants called in MLH1, MSH2, MSH6, and
PMS2 genes were cross-referenced to the International Society for Gastrointestinal Hereditary Tumors Incorporated (InSiGHT) variant database (http://www.insight-group.
In summary, we presented a very rare case of gastric medullary carcinoma with sporadic mismatch repair deficiency for MLH1 and
PMS2, wild-type BRAF gene, and a TP53 c.817C>T (p.R273C) gene mutation.
The gene with the most exon failures was
PMS2 (exons 2, 3, 4, 5, 12, 14, and 15); however, no
PMS2 exons with inadequate coverage were seen in the TruSeq data set.
Although CRCs with isolated loss of
PMS2 staining represent a molecularly heterogeneous group, the underlying molecular alterations resulting in this phenotype are often unknown in day-to-day practice.
The protocol enables sequencing of 255 kb DNA from 94 genes including MLH1, MSH2, MSH6, and
PMS2,as well as 284 single nucleotide polymorphisms using 4000 80-mer probes designed from the human NCBI2137/hg19 reference genome.
The first is the nonpolyposis (hereditary nonpolypoid colon cancer (HNPCC) with its two types: Lynch I & II), which is an autosomal dominant disease that occurs due to mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and
PMS2 which is known to be positive in around 1%-3% in the West, meanwhile it is 4.7% in Iran for example!
The MMR system, comprising 6 proteins (MutL protein homolog, MLH1; MutS protein homologs, MSH2, MSH3, and MSH6; PMS1 protein homolog, PMS1; and MMR endonuclease,
PMS2) and the corresponding genes, recognizes and repairs errors that occur during DNA replication.
Lynch syndrome and hereditary nonpolyposis colorectal cancer (HNPCC) syndrome are due to inherited mutations in one of the mismatch repair genes (including MLH1, MSH2, and
PMS2).
coli) (MLH1), (4) DNA mismatch repair protein Msh2 (MSH2), mutS homolog 6 (MSH6), mismatch repair endonuclease
PMS2 (
PMS2), and epithelial cell adhesion molecule (EPCAM), such as occurs in patients with Lynch syndrome, for whom more than 90% of colon cancers test MSI positive (1, 2).
The blood test offering for Lynch syndrome comprises a blood test panel assessing the genes MLH1, MSH2 (and EPCAM terminal deletions), MSH6 and
PMS2 for inherited mutations that cause most of Lynch syndrome cases.
--Loss of nuclear expression of MLH1 and
PMS2: testing for methylation of the MLH1 promoter is indicated (the presence of MLH1 methylation suggests that the tumor is sporadic and germline evaluation is probably not indicated; absence of MLH1 methylation suggests the possibility of Lynch syndrome, and sequencing and/or large deletion/duplication testing of germline MLH1 is indicated) *
LS is an autosomal dominant disorder caused by germ line-inactivating mutations in one of the 4 DNA mismatch-repair (MMR) genes: MLH14 (mutL homolog 1), MSH2 (mutS homolog 2), MSH6 (mutS homolog 6), and
PMS2 [postmeiotic segregation increased 2 (S.
