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Am J Hum Genet. Oct 1994; 55(4): 666–677.
PMCID: PMC1918278

A Common Region of Deletion on Chromosome 17q in Both Sporadic and Familial Epithelial Ovarian Tumors Distal to BRCA1


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 17pl3.1 and 17pl3.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17ql2-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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  • Anderson LA, Friedman L, Osborne-Lawrence S, Lynch E, Weissenbach J, Bowcock A, King MC. High-density genetic map of the BRCA1 region of chromosome 17q12-q21. Genomics. 1993 Sep;17(3):618–623. [PubMed]
  • Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, Soper JT, Dodge R, Clarke-Pearson DL, Marks P, et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res. 1990 Jul 1;50(13):4087–4091. [PubMed]
  • Bevilacqua G, Sobel ME, Liotta LA, Steeg PS. Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. Cancer Res. 1989 Sep 15;49(18):5185–5190. [PubMed]
  • Bowcock AM, Anderson LA, Friedman LS, Black DM, Osborne-Lawrence S, Rowell SE, Hall JM, Solomon E, King MC. THRA1 and D17S183 flank an interval of < 4 cM for the breast-ovarian cancer gene (BRCA1) on chromosome 17q21. Am J Hum Genet. 1993 Apr;52(4):718–722. [PMC free article] [PubMed]
  • Carrozzo R, Ledbetter DH. Dinucleotide repeat polymorphism mapping to the critical region for lissencephaly (17p13.3). Hum Mol Genet. 1993 May;2(5):615–615. [PubMed]
  • Collins FS, O'Connell P, Ponder BA, Seizinger BR. Progress towards identifying the neurofibromatosis (NF1) gene. Trends Genet. 1989 Jul;5(7):217–221. [PubMed]
  • Easton DF, Bishop DT, Ford D, Crockford GP. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1993 Apr;52(4):678–701. [PMC free article] [PubMed]
  • Eccles DM, Cranston G, Steel CM, Nakamura Y, Leonard RC. Allele losses on chromosome 17 in human epithelial ovarian carcinoma. Oncogene. 1990 Oct;5(10):1599–1601. [PubMed]
  • Eccles DM, Russell SE, Haites NE, Atkinson R, Bell DW, Gruber L, Hickey I, Kelly K, Kitchener H, Leonard R, et al. Early loss of heterozygosity on 17q in ovarian cancer. The Abe Ovarian Cancer Genetics Group. Oncogene. 1992 Oct;7(10):2069–2072. [PubMed]
  • Ehlen T, Dubeau L. Loss of heterozygosity on chromosomal segments 3p, 6q and 11p in human ovarian carcinomas. Oncogene. 1990 Feb;5(2):219–223. [PubMed]
  • Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. [PubMed]
  • Feunteun J, Narod SA, Lynch HT, Watson P, Conway T, Lynch J, Parboosingh J, O'Connell P, White R, Lenoir GM. A breast-ovarian cancer susceptibility gene maps to chromosome 17q21. Am J Hum Genet. 1993 Apr;52(4):736–742. [PMC free article] [PubMed]
  • Flejter WL, Kukowska-Latallo JF, Kiousis S, Chandrasekharappa SC, King SE, Chamberlain JS. Tetranucleotide repeat polymorphism at D17S846 maps within 40 kb of GAS at 17q12-q22. Hum Mol Genet. 1993 Jul;2(7):1080–1080. [PubMed]
  • Foulkes W. Tumour suppressor genes in ovarian cancer. BMJ. 1993 Oct 16;307(6910):1009–1009. [PMC free article] [PubMed]
  • Foulkes WD, Black DM, Stamp GW, Solomon E, Trowsdale J. Very frequent loss of heterozygosity throughout chromosome 17 in sporadic ovarian carcinoma. Int J Cancer. 1993 May 8;54(2):220–225. [PubMed]
  • Futreal PA, Söderkvist P, Marks JR, Iglehart JD, Cochran C, Barrett JC, Wiseman RW. Detection of frequent allelic loss on proximal chromosome 17q in sporadic breast carcinoma using microsatellite length polymorphisms. Cancer Res. 1992 May 1;52(9):2624–2627. [PubMed]
  • Goldgar DE, Cannon-Albright LA, Oliphant A, Ward JH, Linker G, Swensen J, Tran TD, Fields P, Uharriet P, Skolnick MH. Chromosome 17q linkage studies of 18 Utah breast cancer kindreds. Am J Hum Genet. 1993 Apr;52(4):743–748. [PMC free article] [PubMed]
  • Hall JM, Friedman L, Guenther C, Lee MK, Weber JL, Black DM, King MC. Closing in on a breast cancer gene on chromosome 17q. Am J Hum Genet. 1992 Jun;50(6):1235–1242. [PMC free article] [PubMed]
  • Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990 Dec 21;250(4988):1684–1689. [PubMed]
  • Jacobs IJ, Smith SA, Wiseman RW, Futreal PA, Harrington T, Osborne RJ, Leech V, Molyneux A, Berchuck A, Ponder BA, et al. A deletion unit on chromosome 17q in epithelial ovarian tumors distal to the familial breast/ovarian cancer locus. Cancer Res. 1993 Mar 15;53(6):1218–1221. [PubMed]
  • Jolly KW, Malkin D, Douglass EC, Brown TF, Sinclair AE, Look AT. Splice-site mutation of the p53 gene in a family with hereditary breast-ovarian cancer. Oncogene. 1994 Jan;9(1):97–102. [PubMed]
  • Jones MH, Nakamura Y. Detection of loss of heterozygosity at the human TP53 locus using a dinucleotide repeat polymorphism. Genes Chromosomes Cancer. 1992 Jul;5(1):89–90. [PubMed]
  • Kelsell DP, Black DM, Bishop DT, Spurr NK. Genetic analysis of the BRCA1 region in a large breast/ovarian family: refinement of the minimal region containing BRCA1. Hum Mol Genet. 1993 Nov;2(11):1823–1828. [PubMed]
  • King MC. Breast cancer genes: how many, where and who are they? Nat Genet. 1992 Oct;2(2):89–90. [PubMed]
  • King MC, Rowell S, Love SM. Inherited breast and ovarian cancer. What are the risks? What are the choices? JAMA. 1993 Apr 21;269(15):1975–1980. [PubMed]
  • Knudson AG. All in the (cancer) family. Nat Genet. 1993 Oct;5(2):103–104. [PubMed]
  • Kohler MF, Marks JR, Wiseman RW, Jacobs IJ, Davidoff AM, Clarke-Pearson DL, Soper JT, Bast RC, Jr, Berchuck A. Spectrum of mutation and frequency of allelic deletion of the p53 gene in ovarian cancer. J Natl Cancer Inst. 1993 Sep 15;85(18):1513–1519. [PubMed]
  • Lee JH, Kavanagh JJ, Wildrick DM, Wharton JT, Blick M. Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas. Cancer Res. 1990 May 1;50(9):2724–2728. [PubMed]
  • Lindblom A, Skoog L, Rotstein S, Werelius B, Larsson C, Nordenskjöld M. Loss of heterozygosity in familial breast carcinomas. Cancer Res. 1993 Sep 15;53(18):4356–4361. [PubMed]
  • Lobaccaro JM, Lumbroso S, Belon C, Galtier-Dereure F, Bringer J, Lesimple T, Heron JF, Pujol H, Sultan C. Male breast cancer and the androgen receptor gene. Nat Genet. 1993 Oct;5(2):109–110. [PubMed]
  • Lynch HT, Watson P, Conway TA, Lynch JF, Slominski-Caster SM, Narod SA, Feunteun J, Lenoir G. DNA screening for breast/ovarian cancer susceptibility based on linked markers. A family study. Arch Intern Med. 1993 Sep 13;153(17):1979–1987. [PubMed]
  • Malkin D, Li FP, Strong LC, Fraumeni JF, Jr, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, et al. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990 Nov 30;250(4985):1233–1238. [PubMed]
  • Marks JR, Davidoff AM, Kerns BJ, Humphrey PA, Pence JC, Dodge RK, Clarke-Pearson DL, Iglehart JD, Bast RC, Jr, Berchuck A. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res. 1991 Jun 1;51(11):2979–2984. [PubMed]
  • Milner BJ, Allan LA, Kelly KF, Cruickshank D, Hall M, Johnston A, Kitchener H, Parkin D, Haites N. Linkage studies with 17q and 18q markers in a breast/ovarian cancer family. Am J Hum Genet. 1993 Apr;52(4):761–766. [PMC free article] [PubMed]
  • Narod SA, Feunteun J, Lynch HT, Watson P, Conway T, Lynch J, Lenoir GM. Familial breast-ovarian cancer locus on chromosome 17q12-q23. Lancet. 1991 Jul 13;338(8759):82–83. [PubMed]
  • Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, et al. Mutations in the p53 gene occur in diverse human tumour types. Nature. 1989 Dec 7;342(6250):705–708. [PubMed]
  • O'Connell P, Plaetke R, Matsunami N, Odelberg S, Jorde L, Chance P, Leppert M, Lalouel JM, White R. An extended genetic linkage map and an "index" map for human chromosome 17. Genomics. 1993 Jan;15(1):38–47. [PubMed]
  • Okamoto A, Sameshima Y, Yokoyama S, Terashima Y, Sugimura T, Terada M, Yokota J. Frequent allelic losses and mutations of the p53 gene in human ovarian cancer. Cancer Res. 1991 Oct 1;51(19):5171–5176. [PubMed]
  • Oliphant AR, Wright EC, Swensen J, Gruis NA, Goldgar D, Skolnick MH. Dinucleotide repeat polymorphism at the D17S513 locus. Nucleic Acids Res. 1991 Sep 11;19(17):4794–4794. [PMC free article] [PubMed]
  • Phillips N, Ziegler M, Saha B, Xynos F. Allelic loss on chromosome 17 in human ovarian cancer. Int J Cancer. 1993 Apr 22;54(1):85–91. [PubMed]
  • Russell SE, Hickey GI, Lowry WS, White P, Atkinson RJ. Allele loss from chromosome 17 in ovarian cancer. Oncogene. 1990 Oct;5(10):1581–1583. [PubMed]
  • Saito H, Inazawa J, Saito S, Kasumi F, Koi S, Sagae S, Kudo R, Saito J, Noda K, Nakamura Y. Detailed deletion mapping of chromosome 17q in ovarian and breast cancers: 2-cM region on 17q21.3 often and commonly deleted in tumors. Cancer Res. 1993 Jul 15;53(14):3382–3385. [PubMed]
  • Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science. 1989 May 12;244(4905):707–712. [PubMed]
  • Sato T, Akiyama F, Sakamoto G, Kasumi F, Nakamura Y. Accumulation of genetic alterations and progression of primary breast cancer. Cancer Res. 1991 Nov 1;51(21):5794–5799. [PubMed]
  • Sato T, Saito H, Morita R, Koi S, Lee JH, Nakamura Y. Allelotype of human ovarian cancer. Cancer Res. 1991 Oct 1;51(19):5118–5122. [PubMed]
  • Simard J, Feunteun J, Lenoir G, Tonin P, Normand T, Luu The V, Vivier A, Lasko D, Morgan K, Rouleau GA, et al. Genetic mapping of the breast-ovarian cancer syndrome to a small interval on chromosome 17q12-21: exclusion of candidate genes EDH17B2 and RARA. Hum Mol Genet. 1993 Aug;2(8):1193–1199. [PubMed]
  • Smith SA, Easton DF, Evans DG, Ponder BA. Allele losses in the region 17q12-21 in familial breast and ovarian cancer involve the wild-type chromosome. Nat Genet. 1992 Oct;2(2):128–131. [PubMed]
  • Smith SA, Easton DF, Ford D, Peto J, Anderson K, Averill D, Stratton M, Ponder M, Pye C, Ponder BA. Genetic heterogeneity and localization of a familial breast-ovarian cancer gene on chromosome 17q12-q21. Am J Hum Genet. 1993 Apr;52(4):767–776. [PMC free article] [PubMed]
  • Tavassoli M, Ruhrberg C, Beaumont V, Reynolds K, Kirkham N, Collins WP, Farzaneh F. Whole chromosome 17 loss in ovarian cancer. Genes Chromosomes Cancer. 1993 Nov;8(3):195–198. [PubMed]
  • Tonin P, Ehrenborg E, Lenoir G, Feunteun J, Lynch H, Morgan K, Zazzi H, Vivier A, Pollak M, Huynh H, et al. The human insulin-like growth factor-binding protein 4 gene maps to chromosome region 17q12-q21.1 and is close to the gene for hereditary breast-ovarian cancer. Genomics. 1993 Nov;18(2):414–417. [PubMed]
  • Varesco L, Caligo MA, Simi P, Black DM, Nardini V, Casarino L, Rocchi M, Ferrara G, Solomon E, Bevilacqua G. The NM23 gene maps to human chromosome band 17q22 and shows a restriction fragment length polymorphism with BglII. Genes Chromosomes Cancer. 1992 Jan;4(1):84–88. [PubMed]
  • Vile RG. p53: a gene for all tumours? BMJ. 1993 Nov 13;307(6914):1226–1227. [PMC free article] [PubMed]
  • Yang-Feng TL, Han H, Chen KC, Li SB, Claus EB, Carcangiu ML, Chambers SK, Chambers JT, Schwartz PE. Allelic loss in ovarian cancer. Int J Cancer. 1993 Jun 19;54(4):546–551. [PubMed]
  • Zheng JP, Robinson WR, Ehlen T, Yu MC, Dubeau L. Distinction of low grade from high grade human ovarian carcinomas on the basis of losses of heterozygosity on chromosomes 3, 6, and 11 and HER-2/neu gene amplification. Cancer Res. 1991 Aug 1;51(15):4045–4051. [PubMed]
  • Zheng J, Wan M, Zweizig S, Velicescu M, Yu MC, Dubeau L. Histologically benign or low-grade malignant tumors adjacent to high-grade ovarian carcinomas contain molecular characteristics of high-grade carcinomas. Cancer Res. 1993 Sep 15;53(18):4138–4142. [PubMed]
  • Zuppan P, Hall JM, Lee MK, Ponglikitmongkol M, King MC. Possible linkage of the estrogen receptor gene to breast cancer in a family with late-onset disease. Am J Hum Genet. 1991 Jun;48(6):1065–1068. [PMC free article] [PubMed]

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