A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCAI

Andrew K. Godwin, Lisa Vanderveer, David C. Schultz, Henry T. Lynch, Deborah A. Altomare, Kenneth H. Buetow, Mary Daly, Lori A. Getts, Agnes Masny, Norman Rosenblum, Michael Hogan, Robert F. Ozols, Thomas C. Hamilton

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Abstract

Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17q12-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans ∼ 25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene.

Original languageEnglish
Pages (from-to)666-677
Number of pages12
JournalAmerican Journal of Human Genetics
Volume55
Issue number4
StatePublished - 1994

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Chromosome Deletion
Loss of Heterozygosity
Ovarian Neoplasms
Neoplasms
Tumor Suppressor Genes
Chromosomes
BRCA1 Gene
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 7
Carcinogenesis
Breast Neoplasms
DNA

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Godwin, A. K., Vanderveer, L., Schultz, D. C., Lynch, H. T., Altomare, D. A., Buetow, K. H., ... Hamilton, T. C. (1994). A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCAI. American Journal of Human Genetics, 55(4), 666-677.

A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCAI. / Godwin, Andrew K.; Vanderveer, Lisa; Schultz, David C.; Lynch, Henry T.; Altomare, Deborah A.; Buetow, Kenneth H.; Daly, Mary; Getts, Lori A.; Masny, Agnes; Rosenblum, Norman; Hogan, Michael; Ozols, Robert F.; Hamilton, Thomas C.

In: American Journal of Human Genetics, Vol. 55, No. 4, 1994, p. 666-677.

Research output: Contribution to journalArticle

Godwin, AK, Vanderveer, L, Schultz, DC, Lynch, HT, Altomare, DA, Buetow, KH, Daly, M, Getts, LA, Masny, A, Rosenblum, N, Hogan, M, Ozols, RF & Hamilton, TC 1994, 'A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCAI', American Journal of Human Genetics, vol. 55, no. 4, pp. 666-677.
Godwin, Andrew K. ; Vanderveer, Lisa ; Schultz, David C. ; Lynch, Henry T. ; Altomare, Deborah A. ; Buetow, Kenneth H. ; Daly, Mary ; Getts, Lori A. ; Masny, Agnes ; Rosenblum, Norman ; Hogan, Michael ; Ozols, Robert F. ; Hamilton, Thomas C. / A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCAI. In: American Journal of Human Genetics. 1994 ; Vol. 55, No. 4. pp. 666-677.
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abstract = "Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55{\%} (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17q12-q21 were used, LOH was 58{\%} (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73{\%} (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans ∼ 25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene.",
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T1 - A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCAI

AU - Godwin, Andrew K.

AU - Vanderveer, Lisa

AU - Schultz, David C.

AU - Lynch, Henry T.

AU - Altomare, Deborah A.

AU - Buetow, Kenneth H.

AU - Daly, Mary

AU - Getts, Lori A.

AU - Masny, Agnes

AU - Rosenblum, Norman

AU - Hogan, Michael

AU - Ozols, Robert F.

AU - Hamilton, Thomas C.

PY - 1994

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N2 - Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17q12-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans ∼ 25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene.

AB - Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17q12-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans ∼ 25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene.

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