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BRCA1 and BRCA2 mutations in Danish families with hereditary breast and/or ovarian cancer

Thomassen, Mads; Hansen, Thomas V O; Borg, Åke LU ; Lianee, Henriette Theilmann; Wikman, Friedrik; Pedersen, Inge Sokilde; Bisgaard, Marie Luise; Nielsen, Finn C; Kruse, Torben A and Gerdes, Anne-Marie (2008) In Acta Oncologica 47(4). p.772-777
Abstract
A national study of BRCA1 and BRCA2 mutations in Danish HBOC (Hereditary Breast Ovarian Cancer) families revealed a total number of 322 mutation positive families, 206 (64%) BRCA1 and 116 (36%) BRCA2 positive families from a population of 5.5 million inhabitants. Seven hundred and twenty six mutation positive individuals were identified: 402 female BRCAl carriers, 79 male BRCAl carriers, 213 female BRCA2 carriers, and 32 male BRCA2 carriers by April 2006. Most of the mutations were frame shift or nonsense mutations, while large genomic rearrangements were rare. Most mutations were only identified in one family. A few mutations were detected repeatedly. In BRCAl the most common mutations were: 2594delC in 32 families (16%), 3438G > T in... (More)
A national study of BRCA1 and BRCA2 mutations in Danish HBOC (Hereditary Breast Ovarian Cancer) families revealed a total number of 322 mutation positive families, 206 (64%) BRCA1 and 116 (36%) BRCA2 positive families from a population of 5.5 million inhabitants. Seven hundred and twenty six mutation positive individuals were identified: 402 female BRCAl carriers, 79 male BRCAl carriers, 213 female BRCA2 carriers, and 32 male BRCA2 carriers by April 2006. Most of the mutations were frame shift or nonsense mutations, while large genomic rearrangements were rare. Most mutations were only identified in one family. A few mutations were detected repeatedly. In BRCAl the most common mutations were: 2594delC in 32 families (16%), 3438G > T in 19 families (9%), 5382insC in 16 families (8%), 3829delT in 11 families (5%). In BRCA2 the most common mutations were: 6601delA in 13 families (11%), 1538del4 in 12 families (10%), 6714del4 in 10 families (9%). There was a tendency towards a higher frequency of BRCA2 mutations in West Denmark compared to East Denmark. The frequencies of specific BRCA1 and BRCA2 mutations were slightly different in the two regions. The mutations occurring in West Denmark have also been observed in other Scandinavian countries whereas the mutations occurring in East Denmark were more often reported from other European countries and the Baltic countries. The pattern of mutation distributions are comparable with observations from other Scandinavian and European studies and indicate that the Danish BRCAl and BRCA2 mutations are a mixture of Scandinavian mutations and other European mutations including two of the Ashkenazi mutations. Even though a tendency towards founder mutations was observed most mutations were only detected once. Based on these observations we recommend that the mutation screening strategy of the BRCA1 and BRCA2 genes in Danish HBOC families comprises full screening of both genes including analysis for large genomic rearrangements. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Oncologica
volume
47
issue
4
pages
772 - 777
publisher
Taylor & Francis
external identifiers
  • wos:000256886900033
  • scopus:45149114013
ISSN
1651-226X
DOI
10.1080/02841860802004974
language
English
LU publication?
yes
id
f372abf7-acca-4111-8d65-5326e0b6813b (old id 1191243)
date added to LUP
2008-09-08 12:48:03
date last changed
2017-06-25 04:09:45
@article{f372abf7-acca-4111-8d65-5326e0b6813b,
  abstract     = {A national study of BRCA1 and BRCA2 mutations in Danish HBOC (Hereditary Breast Ovarian Cancer) families revealed a total number of 322 mutation positive families, 206 (64%) BRCA1 and 116 (36%) BRCA2 positive families from a population of 5.5 million inhabitants. Seven hundred and twenty six mutation positive individuals were identified: 402 female BRCAl carriers, 79 male BRCAl carriers, 213 female BRCA2 carriers, and 32 male BRCA2 carriers by April 2006. Most of the mutations were frame shift or nonsense mutations, while large genomic rearrangements were rare. Most mutations were only identified in one family. A few mutations were detected repeatedly. In BRCAl the most common mutations were: 2594delC in 32 families (16%), 3438G > T in 19 families (9%), 5382insC in 16 families (8%), 3829delT in 11 families (5%). In BRCA2 the most common mutations were: 6601delA in 13 families (11%), 1538del4 in 12 families (10%), 6714del4 in 10 families (9%). There was a tendency towards a higher frequency of BRCA2 mutations in West Denmark compared to East Denmark. The frequencies of specific BRCA1 and BRCA2 mutations were slightly different in the two regions. The mutations occurring in West Denmark have also been observed in other Scandinavian countries whereas the mutations occurring in East Denmark were more often reported from other European countries and the Baltic countries. The pattern of mutation distributions are comparable with observations from other Scandinavian and European studies and indicate that the Danish BRCAl and BRCA2 mutations are a mixture of Scandinavian mutations and other European mutations including two of the Ashkenazi mutations. Even though a tendency towards founder mutations was observed most mutations were only detected once. Based on these observations we recommend that the mutation screening strategy of the BRCA1 and BRCA2 genes in Danish HBOC families comprises full screening of both genes including analysis for large genomic rearrangements.},
  author       = {Thomassen, Mads and Hansen, Thomas V O and Borg, Åke and Lianee, Henriette Theilmann and Wikman, Friedrik and Pedersen, Inge Sokilde and Bisgaard, Marie Luise and Nielsen, Finn C and Kruse, Torben A and Gerdes, Anne-Marie},
  issn         = {1651-226X},
  language     = {eng},
  number       = {4},
  pages        = {772--777},
  publisher    = {Taylor & Francis},
  series       = {Acta Oncologica},
  title        = {BRCA1 and BRCA2 mutations in Danish families with hereditary breast and/or ovarian cancer},
  url          = {http://dx.doi.org/10.1080/02841860802004974},
  volume       = {47},
  year         = {2008},
}