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Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer

Gentile, Massimilano; Wiman, Åsa; Thorstenson, Sten; Loman, Niklas LU ; Borg, Åke LU and Wingren, Sten (2001) In International Journal of Cancer 92(2). p.208-213
Abstract
Frequent allelic deletions at chromosome 11q24-q25 have been described in both early and late onset breast cancers, suggesting the existence of a gene locus implicated in the initiation and/or progression of the disease. In the present study we fine mapped this region further by loss of heterozygosity (LOH) analysis in a population of early onset breast cancer cases (n = 102, 22 to 36 years old). Loss of chromosomal material was assessed for possible association with patient survival as well as Nottingham histologic grade (NHG). Additionally, we investigated the involvement of the 11q24-q25 locus in a group of familial breast cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n = 32, ages 28 to 40 years). Among the... (More)
Frequent allelic deletions at chromosome 11q24-q25 have been described in both early and late onset breast cancers, suggesting the existence of a gene locus implicated in the initiation and/or progression of the disease. In the present study we fine mapped this region further by loss of heterozygosity (LOH) analysis in a population of early onset breast cancer cases (n = 102, 22 to 36 years old). Loss of chromosomal material was assessed for possible association with patient survival as well as Nottingham histologic grade (NHG). Additionally, we investigated the involvement of the 11q24-q25 locus in a group of familial breast cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n = 32, ages 28 to 40 years). Among the consecutive patients, extensive LOH was observed for all markers at 11q24-q25, with frequencies ranging from 42% to 54%. Deletion at the D11S4125 marker was found to be associated with reduced survival (p = 0.026), whereas the adjacent D11S387 marker correlated with higher histologic grade (p = 0.042). In the familial cases, the most telomeric markers showed substantially lower proportions of LOH, ranging from 10% to 21%. Comparison of the two patient groups demonstrated that this difference in LOH frequency was statistically significant for the D11S4098, D11S968, D11S387 and D11S4125 markers (p = 0.020, p = 0.029, p = 0.0070 and p = 0.0030, respectively). We conclude that 11q25 may harbor a gene implicated in early onset breast cancer. Our data suggest that the most probable position for this locus is defined by the markers D11S387 and D11S4125 and furthermore that it may play a less significant role in familial breast cancer cases not linked to either of the BRCA genes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
11q, LOH, early onset, familial breast cancer, prognosis, young age
in
International Journal of Cancer
volume
92
issue
2
pages
208 - 213
publisher
John Wiley & Sons
external identifiers
  • pmid:11291047
  • wos:000167656800008
  • scopus:0035871994
ISSN
0020-7136
DOI
10.1002/1097-0215(200102)9999:9999<::AID-IJC1169>3.0.CO;2-4
language
English
LU publication?
yes
id
7a0a631c-728c-405f-84a1-6ca544d8e84c (old id 1121215)
date added to LUP
2008-06-27 14:30:25
date last changed
2018-10-03 10:09:37
@article{7a0a631c-728c-405f-84a1-6ca544d8e84c,
  abstract     = {Frequent allelic deletions at chromosome 11q24-q25 have been described in both early and late onset breast cancers, suggesting the existence of a gene locus implicated in the initiation and/or progression of the disease. In the present study we fine mapped this region further by loss of heterozygosity (LOH) analysis in a population of early onset breast cancer cases (n = 102, 22 to 36 years old). Loss of chromosomal material was assessed for possible association with patient survival as well as Nottingham histologic grade (NHG). Additionally, we investigated the involvement of the 11q24-q25 locus in a group of familial breast cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n = 32, ages 28 to 40 years). Among the consecutive patients, extensive LOH was observed for all markers at 11q24-q25, with frequencies ranging from 42% to 54%. Deletion at the D11S4125 marker was found to be associated with reduced survival (p = 0.026), whereas the adjacent D11S387 marker correlated with higher histologic grade (p = 0.042). In the familial cases, the most telomeric markers showed substantially lower proportions of LOH, ranging from 10% to 21%. Comparison of the two patient groups demonstrated that this difference in LOH frequency was statistically significant for the D11S4098, D11S968, D11S387 and D11S4125 markers (p = 0.020, p = 0.029, p = 0.0070 and p = 0.0030, respectively). We conclude that 11q25 may harbor a gene implicated in early onset breast cancer. Our data suggest that the most probable position for this locus is defined by the markers D11S387 and D11S4125 and furthermore that it may play a less significant role in familial breast cancer cases not linked to either of the BRCA genes.},
  author       = {Gentile, Massimilano and Wiman, Åsa and Thorstenson, Sten and Loman, Niklas and Borg, Åke and Wingren, Sten},
  issn         = {0020-7136},
  keyword      = {11q,LOH,early onset,familial breast cancer,prognosis,young age},
  language     = {eng},
  number       = {2},
  pages        = {208--213},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer},
  url          = {http://dx.doi.org/10.1002/1097-0215(200102)9999:9999<::AID-IJC1169>3.0.CO;2-4},
  volume       = {92},
  year         = {2001},
}