Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families: A genetic study of 15 185delAG-mutation kindreds

D. B. Berman, J. Wagner-Costalas, D. C. Schultz, Henry T. Lynch, M. Daly, A. K. Godwin

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

We screened 163 women from breast-ovarian cancer-prone families, as well as 178 individuals affected with breast and/or ovarian cancer but unselected for family history, for germ-line mutations in exon 2 of BRCA1, by SSCP analysis and direct sequencing. A total of 25 mutations were detected. Thirteen of 64 Jewish Ashkenazi women and 2 non-Jewish individuals were found to possess the 185delAG mutation. Haplotype data for all 15 individuals, with markers intragenic to BRCA1, suggest that the Jewish Ashkenazi individuals share a common ancestry that is distinct from the lineage shared by the other two women. These data provide the first evidence of two distinct lines of transmission for the 185delAG mutation, only one of which has its origins in the Jewish Ashkenazi population. Our screening also uncovered 10 affected individuals with an 11-bp deletion at nucleotide 188 of BRCA1 (188del11), 4 of whom are Ashkenazi Jews. This is only the third reported mutation detected within the Jewish Ashkenazi population and may represent the second most common alteration in BRCA1 found in Ashkenazi Jews in the United States. The observed overrepresentation of specific mutations within a subgroup of the general population may eventually contribute to the development of inexpensive and routine tests for BRCA1 mutations, as well as to the elucidation of other contributory factors (e.g., diet, environment, and chemical exposures) that may play a key role in cancer initiation and development. The implications of the mutational data, as well as the role that founder effect, demographic history, and penetrance play in the resulting observed phenomena, are discussed.

Original languageEnglish
Pages (from-to)1166-1176
Number of pages11
JournalAmerican Journal of Human Genetics
Volume58
Issue number6
StatePublished - 1996
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Breast Neoplasms
Mutation
Jews
Population
Founder Effect
Single-Stranded Conformational Polymorphism
Penetrance
Germ-Line Mutation
Haplotypes
Exons
Nucleotides
Demography
Diet
Neoplasms

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families : A genetic study of 15 185delAG-mutation kindreds. / Berman, D. B.; Wagner-Costalas, J.; Schultz, D. C.; Lynch, Henry T.; Daly, M.; Godwin, A. K.

In: American Journal of Human Genetics, Vol. 58, No. 6, 1996, p. 1166-1176.

Research output: Contribution to journalArticle

Berman, D. B. ; Wagner-Costalas, J. ; Schultz, D. C. ; Lynch, Henry T. ; Daly, M. ; Godwin, A. K. / Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families : A genetic study of 15 185delAG-mutation kindreds. In: American Journal of Human Genetics. 1996 ; Vol. 58, No. 6. pp. 1166-1176.
@article{53f0fac262904de8b70c144e7eefacee,
title = "Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families: A genetic study of 15 185delAG-mutation kindreds",
abstract = "We screened 163 women from breast-ovarian cancer-prone families, as well as 178 individuals affected with breast and/or ovarian cancer but unselected for family history, for germ-line mutations in exon 2 of BRCA1, by SSCP analysis and direct sequencing. A total of 25 mutations were detected. Thirteen of 64 Jewish Ashkenazi women and 2 non-Jewish individuals were found to possess the 185delAG mutation. Haplotype data for all 15 individuals, with markers intragenic to BRCA1, suggest that the Jewish Ashkenazi individuals share a common ancestry that is distinct from the lineage shared by the other two women. These data provide the first evidence of two distinct lines of transmission for the 185delAG mutation, only one of which has its origins in the Jewish Ashkenazi population. Our screening also uncovered 10 affected individuals with an 11-bp deletion at nucleotide 188 of BRCA1 (188del11), 4 of whom are Ashkenazi Jews. This is only the third reported mutation detected within the Jewish Ashkenazi population and may represent the second most common alteration in BRCA1 found in Ashkenazi Jews in the United States. The observed overrepresentation of specific mutations within a subgroup of the general population may eventually contribute to the development of inexpensive and routine tests for BRCA1 mutations, as well as to the elucidation of other contributory factors (e.g., diet, environment, and chemical exposures) that may play a key role in cancer initiation and development. The implications of the mutational data, as well as the role that founder effect, demographic history, and penetrance play in the resulting observed phenomena, are discussed.",
author = "Berman, {D. B.} and J. Wagner-Costalas and Schultz, {D. C.} and Lynch, {Henry T.} and M. Daly and Godwin, {A. K.}",
year = "1996",
language = "English",
volume = "58",
pages = "1166--1176",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families

T2 - A genetic study of 15 185delAG-mutation kindreds

AU - Berman, D. B.

AU - Wagner-Costalas, J.

AU - Schultz, D. C.

AU - Lynch, Henry T.

AU - Daly, M.

AU - Godwin, A. K.

PY - 1996

Y1 - 1996

N2 - We screened 163 women from breast-ovarian cancer-prone families, as well as 178 individuals affected with breast and/or ovarian cancer but unselected for family history, for germ-line mutations in exon 2 of BRCA1, by SSCP analysis and direct sequencing. A total of 25 mutations were detected. Thirteen of 64 Jewish Ashkenazi women and 2 non-Jewish individuals were found to possess the 185delAG mutation. Haplotype data for all 15 individuals, with markers intragenic to BRCA1, suggest that the Jewish Ashkenazi individuals share a common ancestry that is distinct from the lineage shared by the other two women. These data provide the first evidence of two distinct lines of transmission for the 185delAG mutation, only one of which has its origins in the Jewish Ashkenazi population. Our screening also uncovered 10 affected individuals with an 11-bp deletion at nucleotide 188 of BRCA1 (188del11), 4 of whom are Ashkenazi Jews. This is only the third reported mutation detected within the Jewish Ashkenazi population and may represent the second most common alteration in BRCA1 found in Ashkenazi Jews in the United States. The observed overrepresentation of specific mutations within a subgroup of the general population may eventually contribute to the development of inexpensive and routine tests for BRCA1 mutations, as well as to the elucidation of other contributory factors (e.g., diet, environment, and chemical exposures) that may play a key role in cancer initiation and development. The implications of the mutational data, as well as the role that founder effect, demographic history, and penetrance play in the resulting observed phenomena, are discussed.

AB - We screened 163 women from breast-ovarian cancer-prone families, as well as 178 individuals affected with breast and/or ovarian cancer but unselected for family history, for germ-line mutations in exon 2 of BRCA1, by SSCP analysis and direct sequencing. A total of 25 mutations were detected. Thirteen of 64 Jewish Ashkenazi women and 2 non-Jewish individuals were found to possess the 185delAG mutation. Haplotype data for all 15 individuals, with markers intragenic to BRCA1, suggest that the Jewish Ashkenazi individuals share a common ancestry that is distinct from the lineage shared by the other two women. These data provide the first evidence of two distinct lines of transmission for the 185delAG mutation, only one of which has its origins in the Jewish Ashkenazi population. Our screening also uncovered 10 affected individuals with an 11-bp deletion at nucleotide 188 of BRCA1 (188del11), 4 of whom are Ashkenazi Jews. This is only the third reported mutation detected within the Jewish Ashkenazi population and may represent the second most common alteration in BRCA1 found in Ashkenazi Jews in the United States. The observed overrepresentation of specific mutations within a subgroup of the general population may eventually contribute to the development of inexpensive and routine tests for BRCA1 mutations, as well as to the elucidation of other contributory factors (e.g., diet, environment, and chemical exposures) that may play a key role in cancer initiation and development. The implications of the mutational data, as well as the role that founder effect, demographic history, and penetrance play in the resulting observed phenomena, are discussed.

UR - http://www.scopus.com/inward/record.url?scp=0029949217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029949217&partnerID=8YFLogxK

M3 - Article

C2 - 8651293

AN - SCOPUS:0029949217

VL - 58

SP - 1166

EP - 1176

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 6

ER -