Abstract
We have analyzed 20 breast-ovarian cancer families, the majority of which show positive evidence of linkage to chromosome 17q12, for germ-line mutations in the BRCA1 gene. BRCA1 mutations cosegregating with breast and ovarian cancer susceptibility were identified in 16 families, including 1 family with a case of male breast cancer. Nine of these mutations have not been reported previously. The majority of mutations were found to generate a premature stop codon leading to the formation of a truncated BRCA1 protein of 2%-88% of the expected normal length. Two mutations altered the RING finger domain. Sequencing of genomic DNA led to the identification of a mutation in the coding region of BRCA1 in 12 families, and cDNA analysis revealed an abnormal or missing BRCA1 transcript in 4 of the 8 remaining families. A total of eight mutations were associated with a reduced quantity of BRCA1 transcript. We were unable to detect BRCA1 mutations in 4 of the 20 families, but only 1 of these was clearly linked to BRCA1. It is expected that the majority of clear examples of the breast-ovarian cancer syndrome will be associated with germ-line mutations in the coding region of BRCA1.
| Original language | English |
|---|---|
| Pages (from-to) | 42-51 |
| Number of pages | 10 |
| Journal | American Journal of Human Genetics |
| Volume | 58 |
| Issue number | 1 |
| State | Published - 1996 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Genetics
Cite this
A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. / Serova, Olga; Montagna, Marco; Torchard, Delphine; Narod, Steven A.; Tonin, Patricia; Sylla, Bakary; Lynch, Henry T.; Feunteun, Jean; Lenoir, Gilbert M.
In: American Journal of Human Genetics, Vol. 58, No. 1, 1996, p. 42-51.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families
AU - Serova, Olga
AU - Montagna, Marco
AU - Torchard, Delphine
AU - Narod, Steven A.
AU - Tonin, Patricia
AU - Sylla, Bakary
AU - Lynch, Henry T.
AU - Feunteun, Jean
AU - Lenoir, Gilbert M.
PY - 1996
Y1 - 1996
N2 - We have analyzed 20 breast-ovarian cancer families, the majority of which show positive evidence of linkage to chromosome 17q12, for germ-line mutations in the BRCA1 gene. BRCA1 mutations cosegregating with breast and ovarian cancer susceptibility were identified in 16 families, including 1 family with a case of male breast cancer. Nine of these mutations have not been reported previously. The majority of mutations were found to generate a premature stop codon leading to the formation of a truncated BRCA1 protein of 2%-88% of the expected normal length. Two mutations altered the RING finger domain. Sequencing of genomic DNA led to the identification of a mutation in the coding region of BRCA1 in 12 families, and cDNA analysis revealed an abnormal or missing BRCA1 transcript in 4 of the 8 remaining families. A total of eight mutations were associated with a reduced quantity of BRCA1 transcript. We were unable to detect BRCA1 mutations in 4 of the 20 families, but only 1 of these was clearly linked to BRCA1. It is expected that the majority of clear examples of the breast-ovarian cancer syndrome will be associated with germ-line mutations in the coding region of BRCA1.
AB - We have analyzed 20 breast-ovarian cancer families, the majority of which show positive evidence of linkage to chromosome 17q12, for germ-line mutations in the BRCA1 gene. BRCA1 mutations cosegregating with breast and ovarian cancer susceptibility were identified in 16 families, including 1 family with a case of male breast cancer. Nine of these mutations have not been reported previously. The majority of mutations were found to generate a premature stop codon leading to the formation of a truncated BRCA1 protein of 2%-88% of the expected normal length. Two mutations altered the RING finger domain. Sequencing of genomic DNA led to the identification of a mutation in the coding region of BRCA1 in 12 families, and cDNA analysis revealed an abnormal or missing BRCA1 transcript in 4 of the 8 remaining families. A total of eight mutations were associated with a reduced quantity of BRCA1 transcript. We were unable to detect BRCA1 mutations in 4 of the 20 families, but only 1 of these was clearly linked to BRCA1. It is expected that the majority of clear examples of the breast-ovarian cancer syndrome will be associated with germ-line mutations in the coding region of BRCA1.
UR - http://www.scopus.com/inward/record.url?scp=0029655346&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029655346&partnerID=8YFLogxK
M3 - Article
C2 - 8554067
AN - SCOPUS:0029655346
VL - 58
SP - 42
EP - 51
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -