Abstract
The 11q13 chromosomal region encodes oncogenes relevant to a variety of human cancers as well as a tumour suppressor gene implicated in multiple endocrine neoplasia type 1. In addition, high affinity folate receptor (FOLR1), which maps to 11q13.3-13.5, is expressed at an elevated level on the surface of over 80% of nonmucinous epithelial ovarian cancers. Further telomeric, 11q breakpoints are found in many cancers. We studied the involvement of 11q markers in ovarian cancer by looking for tumour-specific loss of heterozygosity (LOH), as well as amplification or rearrangements that might explain the overexpression of FOLR1. Twenty eight epithelial ovarian cancers, along with lymphocyte DNA from the same individual were used for Southern blotting with polymorphic probes from 11q. PCR primers from 11q23.3 were also used. The 11q13 band was amplified in four out of 28 cancers. The amplicon included the probe D11S146 as well as FGF3 (formerly INT2) and FOLR1 in one out of these four cases, thus crossing the bcl1 translocation breakpoint. LOH was seen in three out of 16 cases with FGF3 (11q13). A much higher frequency of LOH (8/12) was found at 11q23.3-qter, implying the presence of a tumour suppressor gene in this region.
Full text
PDF





Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bello M. J., Rey J. A. Chromosome aberrations in metastatic ovarian cancer: relationship with abnormalities in primary tumors. Int J Cancer. 1990 Jan 15;45(1):50–54. doi: 10.1002/ijc.2910450111. [DOI] [PubMed] [Google Scholar]
- Campbell I. G., Jones T. A., Foulkes W. D., Trowsdale J. Folate-binding protein is a marker for ovarian cancer. Cancer Res. 1991 Oct 1;51(19):5329–5338. [PubMed] [Google Scholar]
- Chenevix-Trench G., Leary J., Kerr J., Michel J., Kefford R., Hurst T., Parsons P. G., Friedlander M., Khoo S. K. Frequent loss of heterozygosity on chromosome 18 in ovarian adenocarcinoma which does not always include the DCC locus. Oncogene. 1992 Jun;7(6):1059–1065. [PubMed] [Google Scholar]
- Coney L. R., Tomassetti A., Carayannopoulos L., Frasca V., Kamen B. A., Colnaghi M. I., Zurawski V. R., Jr Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein. Cancer Res. 1991 Nov 15;51(22):6125–6132. [PubMed] [Google Scholar]
- Eccles D. M., Cranston G., Steel C. M., Nakamura Y., Leonard R. C. Allele losses on chromosome 17 in human epithelial ovarian carcinoma. Oncogene. 1990 Oct;5(10):1599–1601. [PubMed] [Google Scholar]
- 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] [Google Scholar]
- Elwood P. C. Molecular cloning and characterization of the human folate-binding protein cDNA from placenta and malignant tissue culture (KB) cells. J Biol Chem. 1989 Sep 5;264(25):14893–14901. [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Foroud T., Wei S., Ziv Y., Sobel E., Lange E., Chao A., Goradia T., Huo Y., Tolun A., Chessa L. Localization of an ataxia-telangiectasia locus to a 3-cM interval on chromosome 11q23: linkage analysis of 111 families by an international consortium. Am J Hum Genet. 1991 Dec;49(6):1263–1279. [PMC free article] [PubMed] [Google Scholar]
- Foulkes W., Black D., Solomon E., Trowsdale J. Allele loss on chromosome 17q in sporadic ovarian cancer. Lancet. 1991 Aug 17;338(8764):444–445. doi: 10.1016/0140-6736(91)91065-3. [DOI] [PubMed] [Google Scholar]
- Friedman E., Sakaguchi K., Bale A. E., Falchetti A., Streeten E., Zimering M. B., Weinstein L. S., McBride W. O., Nakamura Y., Brandi M. L. Clonality of parathyroid tumors in familial multiple endocrine neoplasia type 1. N Engl J Med. 1989 Jul 27;321(4):213–218. doi: 10.1056/NEJM198907273210402. [DOI] [PubMed] [Google Scholar]
- Fujimori M., Wells S. A., Jr, Nakamura Y. Fine-scale mapping of the gene responsible for multiple endocrine neoplasia type 1 (MEN 1). Am J Hum Genet. 1992 Feb;50(2):399–403. [PMC free article] [PubMed] [Google Scholar]
- Futreal P. A., Söderkvist P., Marks J. R., Iglehart J. D., Cochran C., Barrett J. C., Wiseman R. W. 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] [Google Scholar]
- Goelz S. E., Hamilton S. R., Vogelstein B. Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. Biochem Biophys Res Commun. 1985 Jul 16;130(1):118–126. doi: 10.1016/0006-291x(85)90390-0. [DOI] [PubMed] [Google Scholar]
- Hecht F. The fragile site hypothesis of cancer. Cancer Genet Cytogenet. 1988 Mar;31(1):119–121. doi: 10.1016/0165-4608(88)90019-2. [DOI] [PubMed] [Google Scholar]
- Heutink P., van der Mey A. G., Sandkuijl L. A., van Gils A. P., Bardoel A., Breedveld G. J., van Vliet M., van Ommen G. J., Cornelisse C. J., Oostra B. A. A gene subject to genomic imprinting and responsible for hereditary paragangliomas maps to chromosome 11q23-qter. Hum Mol Genet. 1992 Apr;1(1):7–10. doi: 10.1093/hmg/1.1.7. [DOI] [PubMed] [Google Scholar]
- Jenkyn D. J., McCartney A. J. A chromosome study of three ovarian tumors. Cancer Genet Cytogenet. 1987 Jun;26(2):327–337. doi: 10.1016/0165-4608(87)90067-7. [DOI] [PubMed] [Google Scholar]
- Lammie G. A., Peters G. Chromosome 11q13 abnormalities in human cancer. Cancer Cells. 1991 Nov;3(11):413–420. [PubMed] [Google Scholar]
- Larsson C., Skogseid B., Oberg K., Nakamura Y., Nordenskjöld M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988 Mar 3;332(6159):85–87. doi: 10.1038/332085a0. [DOI] [PubMed] [Google Scholar]
- Lee J. H., Kavanagh J. J., Wharton J. T., Wildrick D. M., Blick M. Allele loss at the c-Ha-ras1 locus in human ovarian cancer. Cancer Res. 1989 Mar 1;49(5):1220–1222. [PubMed] [Google Scholar]
- Lee J. H., Kavanagh J. J., Wildrick D. M., Wharton J. T., 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] [Google Scholar]
- Li S. B., Schwartz P. E., Lee W. H., Yang-Feng T. L. Allele loss at the retinoblastoma locus in human ovarian cancer. J Natl Cancer Inst. 1991 May 1;83(9):637–640. doi: 10.1093/jnci/83.9.637. [DOI] [PubMed] [Google Scholar]
- Miotti S., Canevari S., Ménard S., Mezzanzanica D., Porro G., Pupa S. M., Regazzoni M., Tagliabue E., Colnaghi M. I. Characterization of human ovarian carcinoma-associated antigens defined by novel monoclonal antibodies with tumor-restricted specificity. Int J Cancer. 1987 Mar 15;39(3):297–303. doi: 10.1002/ijc.2910390306. [DOI] [PubMed] [Google Scholar]
- Motokura T., Bloom T., Kim H. G., Jüppner H., Ruderman J. V., Kronenberg H. M., Arnold A. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 1991 Apr 11;350(6318):512–515. doi: 10.1038/350512a0. [DOI] [PubMed] [Google Scholar]
- Pejovic T., Heim S., Mandahl N., Baldetorp B., Elmfors B., Flodérus U. M., Furgyik S., Helm G., Himmelmann A., Willén H. Chromosome aberrations in 35 primary ovarian carcinomas. Genes Chromosomes Cancer. 1992 Jan;4(1):58–68. doi: 10.1002/gcc.2870040108. [DOI] [PubMed] [Google Scholar]
- Pejovic T., Heim S., Mandahl N., Elmfors B., Flodérus U. M., Furgyik S., Helm G., Willén H., Mitelman F. Consistent occurrence of a 19p+ marker chromosome and loss of 11p material in ovarian seropapillary cystadenocarcinomas. Genes Chromosomes Cancer. 1989 Nov;1(2):167–171. doi: 10.1002/gcc.2870010210. [DOI] [PubMed] [Google Scholar]
- Pejovic T., Heim S., Mandahl N., Elmfors B., Flodérus U. M., Furgyik S., Helm G., Willén H., Mitelman F. Trisomy 12 is a consistent chromosomal aberration in benign ovarian tumors. Genes Chromosomes Cancer. 1990 May;2(1):48–52. doi: 10.1002/gcc.2870020109. [DOI] [PubMed] [Google Scholar]
- Ragoussis J., Senger G., Trowsdale J., Campbell I. G. Genomic organization of the human folate receptor genes on chromosome 11q13. Genomics. 1992 Oct;14(2):423–430. doi: 10.1016/s0888-7543(05)80236-8. [DOI] [PubMed] [Google Scholar]
- Ratnam M., Marquardt H., Duhring J. L., Freisheim J. H. Homologous membrane folate binding proteins in human placenta: cloning and sequence of a cDNA. Biochemistry. 1989 Oct 3;28(20):8249–8254. doi: 10.1021/bi00446a042. [DOI] [PubMed] [Google Scholar]
- Rosenberg C. L., Kim H. G., Shows T. B., Kronenberg H. M., Arnold A. Rearrangement and overexpression of D11S287E, a candidate oncogene on chromosome 11q13 in benign parathyroid tumors. Oncogene. 1991 Mar;6(3):449–453. [PubMed] [Google Scholar]
- Russell S. E., Hickey G. I., Lowry W. S., White P., Atkinson R. J. Allele loss from chromosome 17 in ovarian cancer. Oncogene. 1990 Oct;5(10):1581–1583. [PubMed] [Google Scholar]
- Sasano H., Garrett C. T., Wilkinson D. S., Silverberg S., Comerford J., Hyde J. Protooncogene amplification and tumor ploidy in human ovarian neoplasms. Hum Pathol. 1990 Apr;21(4):382–391. doi: 10.1016/0046-8177(90)90199-f. [DOI] [PubMed] [Google Scholar]
- Sato T., Saito H., Morita R., Koi S., Lee J. H., Nakamura Y. Allelotype of human ovarian cancer. Cancer Res. 1991 Oct 1;51(19):5118–5122. [PubMed] [Google Scholar]
- Schuuring E., Verhoeven E., Mooi W. J., Michalides R. J. Identification and cloning of two overexpressed genes, U21B31/PRAD1 and EMS1, within the amplified chromosome 11q13 region in human carcinomas. Oncogene. 1992 Feb;7(2):355–361. [PubMed] [Google Scholar]
- Srivatsan E. S., Misra B. C., Venugopalan M., Wilczynski S. P. Loss of heterozygosity for alleles on chromosome II in cervical carcinoma. Am J Hum Genet. 1991 Oct;49(4):868–877. [PMC free article] [PubMed] [Google Scholar]
- Srivatsan E. S., Murali V., Seeger R. C. Loss of heterozygosity for alleles on chromosomes 11q and 14q in neuroblastoma. Prog Clin Biol Res. 1991;366:91–98. [PubMed] [Google Scholar]
- Tanigami A., Tokino T., Takiguchi S., Mori M., Glaser T., Park J. W., Jones C., Nakamura Y. Mapping of 262 DNA markers into 24 intervals on human chromosome 11. Am J Hum Genet. 1992 Jan;50(1):56–64. [PMC free article] [PubMed] [Google Scholar]
- Thakker R. V., Bouloux P., Wooding C., Chotai K., Broad P. M., Spurr N. K., Besser G. M., O'Riordan J. L. Association of parathyroid tumors in multiple endocrine neoplasia type 1 with loss of alleles on chromosome 11. N Engl J Med. 1989 Jul 27;321(4):218–224. doi: 10.1056/NEJM198907273210403. [DOI] [PubMed] [Google Scholar]
- Tsao S. W., Mok C. H., Oike K., Muto M., Goodman H. M., Sheets E. E., Berkowitz R. S., Knapp R. C., Lau C. C. Involvement of p53 gene in the allelic deletion of chromosome 17p in human ovarian tumors. Anticancer Res. 1991 Nov-Dec;11(6):1975–1982. [PubMed] [Google Scholar]
- Tsujimoto Y., Jaffe E., Cossman J., Gorham J., Nowell P. C., Croce C. M. Clustering of breakpoints on chromosome 11 in human B-cell neoplasms with the t(11;14) chromosome translocation. Nature. 1985 May 23;315(6017):340–343. doi: 10.1038/315340a0. [DOI] [PubMed] [Google Scholar]
- Viel A., De Pascale L., Toffoli G., Tumiotto L., Miotto E., Boiocchi M. Frequent occurrence of Ha-rasl allelic deletion in human ovarian adenocarcinomas. Tumori. 1991 Feb 28;77(1):16–20. doi: 10.1177/030089169107700104. [DOI] [PubMed] [Google Scholar]
- Warnich L., Groenewald I., Theart L., Retief A. E. Highly informative dinucleotide repeat polymorphism at the D11S29 locus on chromosome 11q23. Hum Genet. 1992 May;89(3):357–359. doi: 10.1007/BF00220560. [DOI] [PubMed] [Google Scholar]
- Weber J. L., Kwitek A. E., May P. E. Dinucleotide repeat polymorphisms at the D11S419 and CD3D loci. Nucleic Acids Res. 1990 Jul 11;18(13):4036–4036. doi: 10.1093/nar/18.13.4036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ziemin-van der Poel S., McCabe N. R., Gill H. J., Espinosa R., 3rd, Patel Y., Harden A., Rubinelli P., Smith S. D., LeBeau M. M., Rowley J. D. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10735–10739. doi: 10.1073/pnas.88.23.10735. [DOI] [PMC free article] [PubMed] [Google Scholar]

