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The 5 ' Region of the MSH2 gene involved in hereditary non-polyposis colorectal cancer contains a high density of recombinogenic sequences

Charbonnier, FC; Baert-Desurmont, S; Liang, P; Di Fiore, F; Martin, C; Frerot, S; Olschwang, S; Wang, Q; Buisine, MP and Gilbert, B, et al. (2005) In Human Mutation 26(3). p.255-261
Abstract
MSH2 rearrangements are involved in approximately 10% of hereditary non,polyposis colorectal cancer (HNPCC) families, and in most of the rearrangements, exon I is deleted. We scanned by quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments (QMPSF) 200 kb of genomic sequences upstream of the MSH2 transcription initiation site in 21 HNPCC families with exon I deletions. This QMPSF scan revealed 12 distinct 5' breakpoints located up to 200 kb upstream of the MSH2 transcription initiation site. Sequencing analysis of the rearranged allele in 17 families revealed that most of the deletions (15/17) resulted from homologous Alu-mediated recombination. QMPSF and sequencing analysis in these 21 families led us to... (More)
MSH2 rearrangements are involved in approximately 10% of hereditary non,polyposis colorectal cancer (HNPCC) families, and in most of the rearrangements, exon I is deleted. We scanned by quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments (QMPSF) 200 kb of genomic sequences upstream of the MSH2 transcription initiation site in 21 HNPCC families with exon I deletions. This QMPSF scan revealed 12 distinct 5' breakpoints located up to 200 kb upstream of the MSH2 transcription initiation site. Sequencing analysis of the rearranged allele in 17 families revealed that most of the deletions (15/17) resulted from homologous Alu-mediated recombination. QMPSF and sequencing analysis in these 21 families led us to detect the presence of 20 distinct 5' breakpoints. In 14 out of 15 Alu-mediated recombinations, we found, either within the identical region in which the recombination had probably occurred or in its vicinity, the 26,bp Alu core sequence containing the recombinogenic Chi-like motif. Compared to the equivalent regions of other human genes, the MSH2 upstream region was found to contain a high density of Alu repeats (30% within 228 kb and 43% within 50 kb), most of which belong to the old Alu S subfamilies. In conclusion, this study demonstrates the heterogeneity of the breakpoints within the MSH2 upstream region and reveals the remarkable density of recombinogenic Alu sequences in this region. (Less)
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publication status
published
subject
keywords
Alu, deletion, QMPSF, HNPCC, MSH2, repeat
in
Human Mutation
volume
26
issue
3
pages
255 - 261
publisher
John Wiley & Sons
external identifiers
  • wos:000231631200011
  • pmid:16086322
  • scopus:24344494026
ISSN
1059-7794
DOI
10.1002/humu.20216
language
English
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yes
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f10f9260-5a82-4092-84d8-c27134761f07 (old id 224948)
date added to LUP
2007-09-21 09:55:51
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2017-01-01 04:21:31
@article{f10f9260-5a82-4092-84d8-c27134761f07,
  abstract     = {MSH2 rearrangements are involved in approximately 10% of hereditary non,polyposis colorectal cancer (HNPCC) families, and in most of the rearrangements, exon I is deleted. We scanned by quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments (QMPSF) 200 kb of genomic sequences upstream of the MSH2 transcription initiation site in 21 HNPCC families with exon I deletions. This QMPSF scan revealed 12 distinct 5' breakpoints located up to 200 kb upstream of the MSH2 transcription initiation site. Sequencing analysis of the rearranged allele in 17 families revealed that most of the deletions (15/17) resulted from homologous Alu-mediated recombination. QMPSF and sequencing analysis in these 21 families led us to detect the presence of 20 distinct 5' breakpoints. In 14 out of 15 Alu-mediated recombinations, we found, either within the identical region in which the recombination had probably occurred or in its vicinity, the 26,bp Alu core sequence containing the recombinogenic Chi-like motif. Compared to the equivalent regions of other human genes, the MSH2 upstream region was found to contain a high density of Alu repeats (30% within 228 kb and 43% within 50 kb), most of which belong to the old Alu S subfamilies. In conclusion, this study demonstrates the heterogeneity of the breakpoints within the MSH2 upstream region and reveals the remarkable density of recombinogenic Alu sequences in this region.},
  author       = {Charbonnier, FC and Baert-Desurmont, S and Liang, P and Di Fiore, F and Martin, C and Frerot, S and Olschwang, S and Wang, Q and Buisine, MP and Gilbert, B and Nilbert, Mef and Lindblom, A and Frebourg, T},
  issn         = {1059-7794},
  keyword      = {Alu,deletion,QMPSF,HNPCC,MSH2,repeat},
  language     = {eng},
  number       = {3},
  pages        = {255--261},
  publisher    = {John Wiley & Sons},
  series       = {Human Mutation},
  title        = {The 5 ' Region of the MSH2 gene involved in hereditary non-polyposis colorectal cancer contains a high density of recombinogenic sequences},
  url          = {http://dx.doi.org/10.1002/humu.20216},
  volume       = {26},
  year         = {2005},
}