PMID- 8808596
OWN - NLM
STAT- MEDLINE
DCOM- 19961121
LR  - 20200824
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 59
IP  - 4
DP  - 1996 Oct
TI  - RNA-based mutation screening in hereditary nonpolyposis colorectal cancer.
PG  - 818-24
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is a cancer syndrome inherited 
      in an autosomal dominant fashion. Four susceptibility genes are known, which code 
      for DNA mismatch repair enzymes. The purpose of this study was to identify the 
      HNPCC gene defects in a cohort of Australian HNPCC families and to evaluate the 
      use of RNA-based screening methods. Six mutations were identified, four in the 
      hMLH1 gene and two in hMSH2, by using a combination of DNA-based and RNA-based 
      methods. One of the hMLH1 defects was a missense mutation, and the other five 
      mutations would be expected to result in a shortened protein. These included a 
      rare type of mRNA splicing mutation in hMLH1 exon 17. By use of 
      reverse-transcriptase (RT) PCR, defective transcripts were detectable for three 
      of the hMLH1 mutations but not for the fourth one, which was predicted to cause 
      skipping of exon 15. Furthermore, many more alternative transcripts for the hMLH1 
      gene were found than previously described, and these were more abundant in the 
      RNA samples prepared from whole blood than from lymphoblastoid cell lines. This 
      confounded RNA-based screening for HNPCC mutations, because it was difficult to 
      determine which aberrant RT-PCR fragment was the real hereditary defect. One of 
      the splice-site mutations reported here causes skipping of exons 9 and 10, which 
      also occurs as an alternative transcript. When the protein-truncation test was 
      used, the results were indistinguishable between the patients in this family and 
      controls. Other aberrant transcripts were also observed that varied in size 
      between individuals but were unrelated to the hereditary defects. This study has 
      important implications for the design of reliable diagnostic tests for HNPCC gene 
      defects.
FAU - Kohonen-Corish, M
AU  - Kohonen-Corish M
AD  - Division of Molecular Medicine, John Curtin School of Medical Research, 
      Australian National University, Canberra. maija.corish@anu.edu.au
FAU - Ross, V L
AU  - Ross VL
FAU - Doe, W F
AU  - Doe WF
FAU - Kool, D A
AU  - Kool DA
FAU - Edkins, E
AU  - Edkins E
FAU - Faragher, I
AU  - Faragher I
FAU - Wijnen, J
AU  - Wijnen J
FAU - Khan, P M
AU  - Khan PM
FAU - Macrae, F
AU  - Macrae F
FAU - St John, D J
AU  - St John DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 63231-63-0 (RNA)
RN  - EC 3.6.1.3 (MSH2 protein, human)
RN  - EC 3.6.1.3 (MutS Homolog 2 Protein)
SB  - IM
MH  - Cell Line
MH  - Cohort Studies
MH  - Colorectal Neoplasms, Hereditary Nonpolyposis/*genetics
MH  - *DNA-Binding Proteins
MH  - Genetic Testing
MH  - Humans
MH  - Lymphocytes/chemistry
MH  - MutS Homolog 2 Protein
MH  - *Mutation
MH  - Polymerase Chain Reaction
MH  - Proteins/genetics
MH  - Proto-Oncogene Proteins/genetics
MH  - RNA/*genetics
PMC - PMC1914793
EDAT- 1996/10/01 00:00
MHDA- 1996/10/01 00:01
PMCR- 1997/04/01
CRDT- 1996/10/01 00:00
PHST- 1996/10/01 00:00 [pubmed]
PHST- 1996/10/01 00:01 [medline]
PHST- 1996/10/01 00:00 [entrez]
PHST- 1997/04/01 00:00 [pmc-release]
PST - ppublish
SO  - Am J Hum Genet. 1996 Oct;59(4):818-24.