A common Greenlandic Inuit BRCA1 RING domain founder mutation

T.v.O. Hansen; B. Ejlertsen; Anders Albrechtsen; E. Bergsten; P. Bjerregaard; T. Hansen; T. Myrhoj; P.B. Nielsen; V. Timmermans-Wielenga; M.K. Andersen; L. Jonson; F.C. Nielsen

A common Greenlandic Inuit BRCA1 RING domain founder mutation

T.v.O. Hansen, B. Ejlertsen, Anders Albrechtsen, E. Bergsten, P. Bjerregaard, T. Hansen, T. Myrhoj, P.B. Nielsen, V. Timmermans-Wielenga, M.K. Andersen, L. Jonson, F.C. Nielsen

16 Citations (Scopus)

Abstract

Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We examined 32 breast and/or ovarian cancer patients from Greenland for mutations in BRCA1 and BRCA2. Whereas no mutations were identified in 19 families, 13 families exhibited a BRCA1 exon 3 nucleotide 234 T > G mutation, which has not previously been reported in the breast cancer information core (BIC) database. The mutation changes a conserved cysteine 39 to a glycine in the Zn(2+) site II of the RING domain, which is essential for BRCA1 ubiquitin ligase activity. Eight of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit, representing almost ~2% of the total Greenlandic Inuit population, showed that the frequency of the mutation was 1.0%. We conclude that the BRCA1 nucleotide 234 T > G is a common Greenlandic Inuit founder mutation. The relative high frequency in the general population, together with the ease of screening and possibility to reduce mortality in gene carriers, may warrant screening of the Greenlandic Inuit population. Provided screening is efficient, about 5% of breast- and 13% of ovarian cancers, respectively, may be prevented
Udgivelsesdato: 2009/5

Original language	English
Journal	Breast Cancer Research and Treatment
Volume	115
Issue number	1
Pages (from-to)	69-76
Number of pages	7
ISSN	0167-6806
Publication status	Published - 2009

Cite this

@article{37530600625e11df928f000ea68e967b,

title = "A common Greenlandic Inuit BRCA1 RING domain founder mutation",

abstract = "Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We examined 32 breast and/or ovarian cancer patients from Greenland for mutations in BRCA1 and BRCA2. Whereas no mutations were identified in 19 families, 13 families exhibited a BRCA1 exon 3 nucleotide 234 T > G mutation, which has not previously been reported in the breast cancer information core (BIC) database. The mutation changes a conserved cysteine 39 to a glycine in the Zn(2+) site II of the RING domain, which is essential for BRCA1 ubiquitin ligase activity. Eight of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit, representing almost ~2% of the total Greenlandic Inuit population, showed that the frequency of the mutation was 1.0%. We conclude that the BRCA1 nucleotide 234 T > G is a common Greenlandic Inuit founder mutation. The relative high frequency in the general population, together with the ease of screening and possibility to reduce mortality in gene carriers, may warrant screening of the Greenlandic Inuit population. Provided screening is efficient, about 5% of breast- and 13% of ovarian cancers, respectively, may be prevented Udgivelsesdato: 2009/5",

author = "T.v.O. Hansen and B. Ejlertsen and Anders Albrechtsen and E. Bergsten and P. Bjerregaard and T. Hansen and T. Myrhoj and P.B. Nielsen and V. Timmermans-Wielenga and M.K. Andersen and L. Jonson and F.C. Nielsen",

year = "2009",

language = "English",

volume = "115",

pages = "69--76",

journal = "Breast Cancer Research and Treatment",

issn = "0167-6806",

publisher = "Springer",

number = "1",

}

TY - JOUR

T1 - A common Greenlandic Inuit BRCA1 RING domain founder mutation

AU - Hansen, T.v.O.

AU - Ejlertsen, B.

AU - Albrechtsen, Anders

AU - Bergsten, E.

AU - Bjerregaard, P.

AU - Hansen, T.

AU - Myrhoj, T.

AU - Nielsen, P.B.

AU - Timmermans-Wielenga, V.

AU - Andersen, M.K.

AU - Jonson, L.

AU - Nielsen, F.C.

PY - 2009

Y1 - 2009

N2 - Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We examined 32 breast and/or ovarian cancer patients from Greenland for mutations in BRCA1 and BRCA2. Whereas no mutations were identified in 19 families, 13 families exhibited a BRCA1 exon 3 nucleotide 234 T > G mutation, which has not previously been reported in the breast cancer information core (BIC) database. The mutation changes a conserved cysteine 39 to a glycine in the Zn(2+) site II of the RING domain, which is essential for BRCA1 ubiquitin ligase activity. Eight of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit, representing almost ~2% of the total Greenlandic Inuit population, showed that the frequency of the mutation was 1.0%. We conclude that the BRCA1 nucleotide 234 T > G is a common Greenlandic Inuit founder mutation. The relative high frequency in the general population, together with the ease of screening and possibility to reduce mortality in gene carriers, may warrant screening of the Greenlandic Inuit population. Provided screening is efficient, about 5% of breast- and 13% of ovarian cancers, respectively, may be prevented Udgivelsesdato: 2009/5

AB - Germ-line mutations in the tumour suppressor proteins BRCA1 and BRCA2 predispose to breast and ovarian cancer. We examined 32 breast and/or ovarian cancer patients from Greenland for mutations in BRCA1 and BRCA2. Whereas no mutations were identified in 19 families, 13 families exhibited a BRCA1 exon 3 nucleotide 234 T > G mutation, which has not previously been reported in the breast cancer information core (BIC) database. The mutation changes a conserved cysteine 39 to a glycine in the Zn(2+) site II of the RING domain, which is essential for BRCA1 ubiquitin ligase activity. Eight of the families had members with ovarian cancer, suggesting that the RING domain may be an ovarian cancer hotspot. By SNP array analysis, we find that all 13 families share a 4.5 Mb genomic fragment containing the BRCA1 gene, showing that the mutation originates from a founder. Finally, analysis of 1152 Inuit, representing almost ~2% of the total Greenlandic Inuit population, showed that the frequency of the mutation was 1.0%. We conclude that the BRCA1 nucleotide 234 T > G is a common Greenlandic Inuit founder mutation. The relative high frequency in the general population, together with the ease of screening and possibility to reduce mortality in gene carriers, may warrant screening of the Greenlandic Inuit population. Provided screening is efficient, about 5% of breast- and 13% of ovarian cancers, respectively, may be prevented Udgivelsesdato: 2009/5

M3 - Journal article

SN - 0167-6806

VL - 115

SP - 69

EP - 76

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

IS - 1

ER -