MLH1, MLH3, PMS1
, and PMS2 are the 4 recognized human MutL homologs.
 Human Genes: KRAS, KRAS proto-oncogene; NRAS, NRAS proto-oncogene; BRAF, B-Raf proto-oncogene; MLH1, mutLhomolog 1; PMS2, PMS1
The specific high-risk genes are BRCA1, BRCA2, RAD51C, RAD51D, and BRIP1, plus Lynch syndrome (MLH1, MSH2, MSH6, PMS1
, and EpCAM), and the minimum surgery for these women is a risk-reducing salpingo-oophorectomy (RRSO).
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.
The distribution of the DNA mismatch repair (MMR) proteins, that is, MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), and PMS1
homolog 2 (PMS2), in the different entities might in addition also be of differential diagnostic and pathogenetic interest.
DNA repair array gene expression results showed that when this patient's results compare with the other NF1 patients without malignancy; ATR, CCNO, MLH1, NEIL1, NTHL1, RAD18, RAD 51, XRCC1, XRCC3 genes are overexpressed and ATM, BRCA1, BRCA2, ERCC4, EXO1, FEN1, LIG1, LIG3, MPG, MRE11A, MSH2, NEIL2, PMS1
, POLD3, RFC1, SMUG1, TDG, TOP3B genes are down-regulated in this patient (mother).
Genes Tested AtP ALK APC ATM BAP1 BRCA2 BRIP1 BUB1B CDC73 CDH1 CEP57 CHEK2 CYLD DDB2 DICER1 ERCC3 ERCC4 ERCC5 EXT1 EXT2 FANCD2 FANCE FANCF FANCG FANCI GATA2 GPC3 HNF1A HOXB13 HRAS MLH1 MHS2 MSH6 MUTYH NBN PHOX2B PMS1
PMS2 PPM1D PRF1 RAD51D RBI RECQL4 RET RHBDF2 SDHC SDHD SLX4 SMAD4 SMARCA4 TP53 TSC1 TSC2 VHL WT1 BARD1 BLM BMPR1A BRCA1 CDK4 CDKN1C CDKN2A CEBPA DI53L2 EGFR EPCAM ERCC2 EZH2 FANCA FANCB FANCC FANCL FANCM FH FLCN KIT MAX MEN1 MET NF1 NF2 NSD1 PALB2 PRKAR1A PTCH1 PTEN RAD51C RUN XI SBDS SDHAF2 SDHB SMARCB1 STK11 5UFU TMEM127 WRN XPA XPC This chart shows all 98 cancer susceptible genes included in this new test.
In humans, at least seven mismatch repair genes are involved in mismatch repair and their names derive from their structural homology to the bacterial proteins: the MutS homologues (MSH), MSH2 on chromosome 2p16, MSH3 on chromosome 5q11, and MSH6 on chromosome 2p16; the MutL homologues (MLH), MLH1 on chromosome 3p21 and MLH3 on chromosome 2p16; the postmeiotic segregation homologues (PMS), PMS1
and PMS2 on chromosome 7p22.
In eukaryotes, multiple homologues of MutS (MSH1-MSH7) and MutL (MLH1-3, PMS1
, and PMS2) have been characterized, but not of MutH.
They determined that the two loci were located on chromosomes 3 and 7, respectively, and the effect of the locus on chromosome 7 (pms1
) was two to three times greater than the one on chromosome 3 (pms2).