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Deletions on chromosome 4 in sporadic and BRCA mutated tumors and association with pathological variables

Johannsdottir, HK; Johannesdottir, G; Agnarsson, BA; Eerola, H; Arason, A; Johannsson, OT; Heikkila, P; Egilsson, V; Olsson, Håkan LU and Borg, Åke LU , et al. (2004) In Anticancer Research 24(5A). p.2681-2687
Abstract
Background: Chromosomal aberrations in breast tumors from BRCA1 and BRCA2 germ-line mutation carriers are considerably more frequent than what is seen in sporadic breast tumors. According to Comparative Genomic Hybridisation analysis (CGH), deletions on chromosome 4 are one of the most frequent events in BRCA1-associated tumors, suggesting inactivation of specific tumor suppressor genes. Materials and Methods: In the present study, 16 microsatellite markers covering chromosome 4 were used to map loss of heterozygosity (LOH) in tumors from BRCA1 (n =41) as well as in tumors from BRCA2 (n = 66) mutation carriers and in tumors from unselected cases of breast cancer (n = 68). Results: The frequency of LOH in these groups ranged from 16-73% in... (More)
Background: Chromosomal aberrations in breast tumors from BRCA1 and BRCA2 germ-line mutation carriers are considerably more frequent than what is seen in sporadic breast tumors. According to Comparative Genomic Hybridisation analysis (CGH), deletions on chromosome 4 are one of the most frequent events in BRCA1-associated tumors, suggesting inactivation of specific tumor suppressor genes. Materials and Methods: In the present study, 16 microsatellite markers covering chromosome 4 were used to map loss of heterozygosity (LOH) in tumors from BRCA1 (n =41) as well as in tumors from BRCA2 (n = 66) mutation carriers and in tumors from unselected cases of breast cancer (n = 68). Results: The frequency of LOH in these groups ranged from 16-73% in BRCA1-associated tumors, 13-42% in BRCA2-associated tumors and 8-33% in unselected tumors. LOH was significantly more frequent in BRCA1-associated tumors as compared to BRCA2-associated tumors and unselected tumors, and particularly high (over 70%) at 4q35.2. Pathological variables that were found significantly associated (pless than or equal to0.05) with LOH at specific markers were: high percentage of cells in S-phase, negative estrogen receptor status, young age at diagnosis and large tumors. Deletion mapping indicates the existence of seven non-overlapping regions at chromosome 4, which were identified in all three groups of tumors. Three of these seven regions, 4p16.3-p16.1, 4q27-q32.1 and 4q35.1-4qter, have not been reported in breast cancer previously. Conclusion: The results manifest the frequent alterations of chromosome 4 in BRCA1-associated breast tumors and indicate the location of several genes of potential importance in breast cancer development. (Less)
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published
subject
keywords
BRCA2, breast cancer, BRCA1, loss of heterozygosity
in
Anticancer Research
volume
24
issue
5A
pages
2681 - 2687
publisher
International Institute of Cancer Research
external identifiers
  • wos:000224629700012
  • scopus:6444240104
ISSN
1791-7530
language
English
LU publication?
yes
id
4523f08f-cca4-4969-b34a-ecd3c4ec791c (old id 262953)
date added to LUP
2007-10-23 12:41:48
date last changed
2017-01-01 04:23:36
@article{4523f08f-cca4-4969-b34a-ecd3c4ec791c,
  abstract     = {Background: Chromosomal aberrations in breast tumors from BRCA1 and BRCA2 germ-line mutation carriers are considerably more frequent than what is seen in sporadic breast tumors. According to Comparative Genomic Hybridisation analysis (CGH), deletions on chromosome 4 are one of the most frequent events in BRCA1-associated tumors, suggesting inactivation of specific tumor suppressor genes. Materials and Methods: In the present study, 16 microsatellite markers covering chromosome 4 were used to map loss of heterozygosity (LOH) in tumors from BRCA1 (n =41) as well as in tumors from BRCA2 (n = 66) mutation carriers and in tumors from unselected cases of breast cancer (n = 68). Results: The frequency of LOH in these groups ranged from 16-73% in BRCA1-associated tumors, 13-42% in BRCA2-associated tumors and 8-33% in unselected tumors. LOH was significantly more frequent in BRCA1-associated tumors as compared to BRCA2-associated tumors and unselected tumors, and particularly high (over 70%) at 4q35.2. Pathological variables that were found significantly associated (pless than or equal to0.05) with LOH at specific markers were: high percentage of cells in S-phase, negative estrogen receptor status, young age at diagnosis and large tumors. Deletion mapping indicates the existence of seven non-overlapping regions at chromosome 4, which were identified in all three groups of tumors. Three of these seven regions, 4p16.3-p16.1, 4q27-q32.1 and 4q35.1-4qter, have not been reported in breast cancer previously. Conclusion: The results manifest the frequent alterations of chromosome 4 in BRCA1-associated breast tumors and indicate the location of several genes of potential importance in breast cancer development.},
  author       = {Johannsdottir, HK and Johannesdottir, G and Agnarsson, BA and Eerola, H and Arason, A and Johannsson, OT and Heikkila, P and Egilsson, V and Olsson, Håkan and Borg, Åke and Nevanlinna, H and Barkardottir, RB},
  issn         = {1791-7530},
  keyword      = {BRCA2,breast cancer,BRCA1,loss of heterozygosity},
  language     = {eng},
  number       = {5A},
  pages        = {2681--2687},
  publisher    = {International Institute of Cancer Research},
  series       = {Anticancer Research},
  title        = {Deletions on chromosome 4 in sporadic and BRCA mutated tumors and association with pathological variables},
  volume       = {24},
  year         = {2004},
}