Abstract
Eight Icelandic breast cancer kindreds were subjected to linkage analyses with respect to 28 microsatellite loci dispersed along the short arm of chromosome 3. Breast tumors derived from these kindreds were concurrently scored for allelic imbalance with ten of the markers. Linkage to most markers could be excluded on the basis of negative LOD scores and haplotype analyses, although some moderately positive LOD scores resulted. A high frequency of imbalance in the familial tumors was seen with two of the markers in comparison with results obtained from sporadic material. The highest frequency (68%) of imbalance was detected with the marker D3S1217, which is located on 3p14.2-p14.1. Imbalance at the D3S1211 locus, which is more telomeric (3p24.2-p22), was not significantly elevated in the familial tumors. We suggest that the genetic defect responsible for breast cancer susceptibility in these families either promotes instability in the 3p14.2-p14.1 region or enhances the selective advantage of such changes.
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References
Arason A, Barkardottir RB, Egilsson V (1993) Linkage analysis of chromosome 17q markers and breast-ovarian cancer in Ice-landic families, and possible relationship to prostatic cancer. Am J Hum Genet 52:711–717
Claus EB, Risch N, Thompson WD (1991) Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum Genet 48:232–242
Cornelisse CJ, Kuipers-Dijkshorn N, Vliet M van, Hermans J, Devilee P (1992) Fractional allelic imbalance in human breast cancer increases with tetraploidization and chromosome loss. Int J Cancer 50:544–548
Devilee P, Broek M van den, Manners M, Slater R, Cornelisse CJ, Westerveld A, Meera Khan P (1991) Differences in patterns of allelic loss between two common types of adult cancer, breast and colon carcinoma, and Wilms' tumor of childhood. Int J Cancer 47:817–821
Easton DF, Bishop DT, Ford D, Crockford GP (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am J Hum Genet 52:678–701
Ehlen T, Dubeau L (1990) Loss of heterozygosity on chromosomal segments 3p, 6q and 11p in human ovarian carcinomas. Oncogene 5:219–223
Eiriksdottir G, Bergthorsson JT, Sigurdsson H, Gudmundsson J, Skirnisdottir S, Egilsson V, Barkardottir RB, Ingvarsson S (1995) Mapping of chromosome 3 alterations in human breast cancer using microsatellite PCR markers: correlation with clinical variables. Int J Oncol 6:369–375
Futreal PA, Liu Q, Shattuck-Eidens D, Cochran C, Harshman K, Tavtigian K, Bennett LM, Haugen-Strano, Swensen J, Miki Y, Eddington K, McClure M, Frye C, Weaver-Feldhaus J, Ding W, Gholami Z, Söderkvist P, Terry L, Jhanwar S, Berchuck A, Iglehart JD, Marks J, Ballinger DG, Barrett JC, Skolnick MH, Kamb A, Wiseman R (1994) BRCA1 mutations in primary breast and ovarian carcinomas. Science 266:120–122
Garcia DK, Sherman S, Leach RJ, Schantz LJ, Huang W, Wolf ME, Chinn RB, Naylor SL (1991) CA repeat polymorphisms for human chromosome 3. Cytogenet Cell Genet 58:1877
Glebov OK, McKenzie KE, White CA, Sukumar S (1994) Frequent gene mutations and novel alleles in familial breast cancer. Cancer Res 54:3703–3709
Gyapay G, Morissette J, Vignal A, Dib C, Fizames C, Millasseau P, Marc S, Bernardi G, Lathrop M, Weissenbach J (1994) The 1993–1994 Généthon human genetic linkage map. Nature Genet 7:246–267
Hall JM, Lee M, Newman B, Morrow JE, Anderson LA, King M-C (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250:1684–1689
Hibi K, Takahashi T, Yamakawa K, Ueda R, Sekido Y, Ariyoshi Y, Suyama M, Takagi H, Nakamura Y, Takahashi T (1992) Three distinct regions involved in 3p deletion in human lung cancer. Oncogene 7:445–449
Huang DP, Lo K-W, Choi PHK, Ng AYT, Tsao S-Y, Yiu GKC, Lee JCK (1991) Loss of heterozygosity on the short arm of chromosome 3 in nasopharyngeal carcinoma. Cancer Genet Cytogenet 54:91–99
Hudson TJ, Engelstein M, Lee MK, Ho EC, Rubenfield MJ, Adams CP, Housman DE, Dracopoli NC (1992) Isolation and chromosomal assignment of 100 highly informative human simple sequence repeat polymorphisms. Genomics 13:622–629
Jackson DP, Lewis FA, Taylor GR, Boylston AW, Quirke P (1990) Tissue analysis of DNA and RNA and analysis by the polymerase chain reaction. J Clin Pathol 43:499–504
Jones MH, Yamakawa Y, Nakamura Y (1992) Isolation and characterization of 19 dinucleotide repeat polymorphisms on chromosome 3p. Hum Molec Genet 1:131–133
Killary AM, Wolf ME, Giambernardi TA, Naylor S (1992) Definition of a tumor suppressor locus within human chromosome 3p21-p22. Proc Natl Acad Sci USA 89:10877–10881
Kovacs G, Erlandsson R, Boldog F, Ingvarsson S, Muller-Brechlin R, Klein G, Sümegi J (1988) Consistent 3p deletion and loss of heterozygosity in renal cell carcinoma. Proc Natl Acad Sci USA 85:1591–1595
Lathrop GM, Lalouel JM (1984) Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet 36:460–465
Latif F, Fivash M, Glenn G, Tory K, Orcutt ML, Hampsch K, Delisio J, Lerman M, Cowan J, Beckett M, Weichselbaum R (1992) Chromosome 3p deletions in head and neck carcinomas: statistical ascertainment of allelic loss. Cancer Res 52:1451–1456
Lothe RA, Fossa SD, Stenwig AE, Nakamura Y, White R, Börresen A-L, Brögger A (1989) Loss of 3p or 11p alleles is associated with testicular cancer tumors. Genomics 5:134–138
Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennet LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, Mclure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A, Skolnick MH (1994) Isolation of BRCA1, the 17q-linked breast and ovarian cancer susceptibility gene. Science 266:66–71
Newman B, Melissa A, Lee M, King M-C (1988) Inheritance of human breast cancer: evidence for autosomal dominant transmission in high risk families. Proc Natl Acad Sci USA 88:3044–3048
Pandis N, Jin Y, Limon J, Bardi G, Idvall I, Mandahl N, Mitelman F, Heim S (1993) Interstitial deletion of the short arm of chromosome 3 as a primary chromosome abnormality in carcinomas of the breast. Genes Chromosom Cancer 6:151–155
Prosser J, Porter D, Coles C (1992) Constitutional p53 mutation in a non-Li-Fraumeni cancer family. Br J Cancer 65:527–528
Sakurai A, Bell GI, DeGroot LJ (1991) Dinucleotide repeat polymorphism in the human thyroid hormone receptor beta gene (THRB) on chromosome 3. Nucleic Acids Res 19:6661
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor laboratory, Cold Spring Harbor, NY
Sato T, Akiyama F, Sakamoto G, Kasumi F, Nakamura Y (1991) Accumulation of genetic alterations and progression of primary breast cancer. Cancer Res 51:5794–5799
Smith SA, Easton DF, Evans DGR, Ponder BAJ (1992) Allele loss in the region 17q12–21 in familial breast and ovarian cancer involve the wild type chromosome. Nature Genet 2:128–131
Srivastava S, Zou Z, Pirollo K, Blattner W, Chang EH (1990) Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature 348:747–749
Takahashi E, Yamakawa K, Nakamura Y, Hori T (1992) A high-resolution cytogenetic map of human chromosome 3: localization of 291 new cosmid markers by direct R-banding fluorescence in situ hybridization. Genomics 13:1047–1055
Weissenbach J, Gyapay G, Dib C, Vignal A, Morissette J, Millasseau P, Vaysseix G, Lathrop M (1992) A second-generation linkage map of the human genome. Nature 359:794–801
Wilkie CM, Guo S-W, Hall BK, Boldog F, Gemmil RM, Chandrasekharappa SC, Barcroft CL, Drabkin HA, Glover TW (1994) Multicolor FISH mapping of YAC clones in 3p14 and identification of a YAC spanning both FRA3B and the t(3;8) associated with hereditary renal cell carcinoma. Genomics 22:319–326
Wooster R, Mangion J, Eeles R, Smith S, Dowsett M, Averill D, Barret-Lee P, Easton F, Ponder BAJ, Stratton MR (1992) A germline mutation in the androgen receptor gene in two brothers with Reifenstein syndrome. Nature Genet 2:132–134
Wooster R, Ford D, Mangion J, Ponder BAJ, Peto J, Easton DF, Stratton MR (1993) Absence of linkage to the ataxia telangiectasia locus in familial breast cancer. Hum Genet 92:91–94
Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D, Fields P, Marshall G, Narod S, Lenoir GM, Lynch H, Feunteun J, Devilee P, Cornelisse CJ, Menko FH, Daly PA, Ormiston W, McManus R, Pye C, Lewis CM, Cannon-Albright LA, Peto J, Ponder BAJ, Skolnick MH, Easton DF, Goldgar DE, Stratton MR (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 265:2088–2090
Yamakawa K, Takahashi E, Morita R, Nakamura Y (1991a) Construction of a genetic linkage map of human chromosome 3, and its application to analysis of renal cell carcinoma. Cytogenet Cell Genet 58:1883
Yamakawa K, Takahashi E, Saito H, Sato T, Oshimura M, Hori T, Nakamura Y (1991b) Isolation and mapping of 75 new DNA markers on human chromosome 3. Genomics 9:536–543
Yamakawa K, Morita R, Takahashi E, Hori T, Lathrop M, Nakamura Y (1991c) Polymorphism markers for human chromosome 3. Genomics 11:565–572
Yokota J, Tsukada Y, Nakajima T, Gotoh M, Shimosato Y, Mori N, Tsunokawa Y, Sugimura T, Terada M (1989) Loss of heterozygosity on the short arm of chromosome 3 in carcinoma of the uterine cervix. Cancer Res 49:3598–3601
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Bergthorsson, J.T., Eiriksdottir, G., Barkardottir, R.B. et al. Linkage analysis and allelic imbalance in human breast cancer kindreds using microsatellite markers from the short arm of chromosome 3. Hum Genet 96, 437–443 (1995). https://doi.org/10.1007/BF00191803
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DOI: https://doi.org/10.1007/BF00191803