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Stability of BAT26 in tumours of hereditary nonpolyposis colorectal cancer patients with MSH2 intragenic deletion
- Source :
- European Journal of Human Genetics. 14:63-68
- Publication Year :
- 2005
- Publisher :
- Springer Science and Business Media LLC, 2005.
-
Abstract
- Colon cancers arising in most patients with hereditary nonpolyposis colorectal cancer (HNPCC) show microsatellite instability (MSI). BAT26, a quasimonomorphic polyA stretch located just 3' of MSH2 exon 5, is considered the most sensitive and specific marker of MSI. A total of 10 HNPCC families with large intragenic MSH2 deletions, encompassing exon 5 and intron 5, identified by multiplex ligation-dependent probe amplification (MLPA) were included in this study. The deletions under study were del1-16, del1-8, del1-7, del1-6, and del3-6, detected in 3, 1, 2, 3, and 1 families, respectively. Although all patients examined from these 10 families developed unstable tumours, 13/19 MSI-H tumours (68 %) surprisingly showed stability of BAT26. By MLPA and MSH2 sequence analyses of the BAT26-stable tumours, we demonstrated that the wild-type MSH2 allele was somatically inactivated by an identical large deletion, with complete loss of intron 5/BAT26 sequences at the tumour DNA level. We could infer that the apparent stability of BAT26 was due to the complete absence of target BAT26 sequences in the tumour sample, which results in exclusive amplification of contaminant normal DNA, containing a single copy of a wild-type stable BAT26 sequence. Identification of a subset of MSH2-related unstable tumours that are not recognized by analysis of BAT26 instability indicates that this marker should never be used alone for rapid MSI screening of HNPCC tumours. Moreover, our findings indicate that BAT26 stability in the context of MSI is strongly suggestive of the presence of a large intragenic MSH2 deletion.
- Subjects :
- Heterozygote
congenital, hereditary, and neonatal diseases and abnormalities
GENES
HNPCC
CELL-LINES
Context (language use)
Biology
Settore MED/03 - GENETICA MEDICA
Exon
MICROSATELLITE-INSTABILITY
MONONUCLEOTIDE REPEATS
FREQUENT CAUSE
Chromosomal Instability
Chromosome instability
GERMLINE
Gene duplication
Genetics
medicine
Humans
Multiplex ligation-dependent probe amplification
neoplasms
GENOMIC DELETIONS
Genetics (clinical)
Sequence Deletion
MLH1
INACTIVATION
nutritional and metabolic diseases
Microsatellite instability
medicine.disease
Colorectal Neoplasms, Hereditary Nonpolyposis
digestive system diseases
MutS Homolog 2 Protein
MSH2
Microsatellite
Poly A
Subjects
Details
- ISSN :
- 14765438 and 10184813
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....dbc4bba7cec595b07b259b1b6d97e72d