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.
En este gen se ha identificado el mayor numero de mutaciones que generan la perdida total del sistema MMR porque, junto con PMS2
, permite la interaccion de las enzimas encargadas de la escision de nucleotidos con las proteinas que reconocen el dano en el ADN (51).
According to the company, the panel of five assays includes four that target MMR proteins MLH1, MSH2, MSH6 and PMS2
, as well as the VENTANA BRAF V600E (VE1) assay.
Many clinically relevant genes (such as PMS2
, STRC) have pseudogenes, are challenging to interpret by NGS, and require specialized methods for target enrichment such as long-range PCR.
MSH2 / MLH1 / MSH6 / PMS2
(in the case of the characteristics of awakening suspicion of Lynch syndrome).
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.
Affected relative with a known genetic mutation (MLH1, MSH2, MSH6, PMS2
Because the clinical criteria used to identify patients with Lynch syndrome suffer from low sensitivity, recent guidelines recommend universal testing of all newly diagnosed CRCs by either microsatellite instability (MSI) analysis or immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2
coli) (MLH1), (4) DNA mismatch repair protein Msh2 (MSH2), mutS homolog 6 (MSH6), mismatch repair endonuclease 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).
69,93) Loss of nuclear staining for both MLH1 and PMS2
is most likely a somatic alteration due to hypermethylation of the MLH1 promoter.
The test is designed to identify a genetic predisposition to HNPCC by analysing MSH2 and its upstream gene EPCAM, as well as the MLH1, MSH6 and PMS2
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.