Stability of BAT26 in tumours of hereditary nonpolyposis colorectal cancer patients with MSH2 intragenic deletion

Chiara Pastrello, Silvana Baglioni, Maria Grazia Tibiletti, Laura Papi, Mara Fornasarig, Alberto Morabito, Marco Agostini, Maurizio Genuardi, Alessandra Viel

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)63-68
Number of pages6
JournalEuropean Journal of Human Genetics
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2006

Keywords

  • BAT26
  • Heredity nonpolyposis colorectal cancer
  • Microsatellite instability
  • Multiplex ligation-dependent probe amplification

ASJC Scopus subject areas

  • Genetics(clinical)

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