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British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(12):1550–1553. doi: 10.1038/bjc.1997.594

Exclusion of BBC1 and CMAR as candidate breast tumour-suppressor genes.

E Moerland 1, M H Breuning 1, C J Cornelisse 1, A M Cleton-Jansen 1
PMCID: PMC2228200  PMID: 9413939

Abstract

Loss of heterozygosity (LOH) on chromosome arm 16q occurs in 48-65% of breast tumours. One small region of overlap is located at 16q24.3. Two genes located in this region, the cellular adhesion regulatory molecule (CMAR) and the breast basic conserved gene (BBC1), are plausible candidate tumour-suppressor genes. Mutational analysis of the retained copy of these genes has been performed by direct sequencing in a selected set of breast tumours that show LOH at 16q24.3 but not at other regions on chromosome arm 16q. In CMAR no other alterations than the previously described 4-bp insertion of CACA at nucleotide 241 could be detected, which was also present in constitutional DNA of the same patients. This polymorphism occurs homozygously in germline DNA of normal individuals and breast cancer patients. LOH analysis at this locus shows no preferential loss of a particular variant of the 241 polymorphism. In the BBC1 gene, three different alterations were found, but only one resulted in an amino acid substitution. This is a known polymorphism, however, also appearing in germline DNA. The absence of tumour-specific mutations in CMAR and BBC1 in this selected series of breast tumours implies that another gene at 16q24.3 must be the tumour-suppressor gene that is the target for LOH in breast cancer.

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Selected References

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  1. Adams S. M., Helps N. R., Sharp M. G., Brammar W. J., Walker R. A., Varley J. M. Isolation and characterization of a novel gene with differential expression in benign and malignant human breast tumours. Hum Mol Genet. 1992 May;1(2):91–96. doi: 10.1093/hmg/1.2.91. [DOI] [PubMed] [Google Scholar]
  2. Bertauche N., Leung J., Giraudat J. Conservation of the human breast basic conserved 1 gene in the plant kingdom: characterization of a cDNA clone from Arabidopsis thaliana. Gene. 1994 Apr 20;141(2):211–214. doi: 10.1016/0378-1119(94)90573-8. [DOI] [PubMed] [Google Scholar]
  3. Cleton-Jansen A. M., Collins N., Lakhani S. R., Weissenbach J., Devilee P., Cornelisse C. J., Stratton M. R. Loss of heterozygosity in sporadic breast tumours at the BRCA2 locus on chromosome 13q12-q13. Br J Cancer. 1995 Nov;72(5):1241–1244. doi: 10.1038/bjc.1995.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cleton-Jansen A. M., Moerland E. W., Kuipers-Dijkshoorn N. J., Callen D. F., Sutherland G. R., Hansen B., Devilee P., Cornelisse C. J. At least two different regions are involved in allelic imbalance on chromosome arm 16q in breast cancer. Genes Chromosomes Cancer. 1994 Feb;9(2):101–107. doi: 10.1002/gcc.2870090205. [DOI] [PubMed] [Google Scholar]
  5. Cleton-Jansen A. M., Moerland H. W., Callen D. F., Doggett N. A., Devilee P., Cornelisse C. J. Mapping of the breast basic conserved gene (D16S444E) to human chromosome band 16q24.3. Cytogenet Cell Genet. 1995;68(1-2):49–51. doi: 10.1159/000133886. [DOI] [PubMed] [Google Scholar]
  6. Dorion-Bonnet F., Mautalen S., Hostein I., Longy M. Allelic imbalance study of 16q in human primary breast carcinomas using microsatellite markers. Genes Chromosomes Cancer. 1995 Nov;14(3):171–181. doi: 10.1002/gcc.2870140304. [DOI] [PubMed] [Google Scholar]
  7. Durbin H., Novelli M., Bodmer W. Detection of a 4-bp insertion (CACA) functional polymorphism at nucleotide 241 of the cellular adhesion regulatory molecule CMAR (formerly CAR). Genomics. 1994 Jan 1;19(1):181–182. doi: 10.1006/geno.1994.1038. [DOI] [PubMed] [Google Scholar]
  8. Koyama K., Emi M., Nakamura Y. The cell adhesion regulator (CAR) gene, TaqI and insertion/deletion polymorphisms, and regional assignment to the peritelomeric region of 16q by linkage analysis. Genomics. 1993 Apr;16(1):264–265. doi: 10.1006/geno.1993.1173. [DOI] [PubMed] [Google Scholar]
  9. Olvera J., Wool I. G. The primary structure of rat ribosomal protein L13. Biochem Biophys Res Commun. 1994 May 30;201(1):102–107. doi: 10.1006/bbrc.1994.1674. [DOI] [PubMed] [Google Scholar]
  10. Pullman W. E., Bodmer W. F. Cloning and characterization of a gene that regulates cell adhesion. Nature. 1992 Apr 9;356(6369):529–532. doi: 10.1038/356529a0. [DOI] [PubMed] [Google Scholar]
  11. Tsuda H., Callen D. F., Fukutomi T., Nakamura Y., Hirohashi S. Allele loss on chromosome 16q24.2-qter occurs frequently in breast cancers irrespectively of differences in phenotype and extent of spread. Cancer Res. 1994 Jan 15;54(2):513–517. [PubMed] [Google Scholar]

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