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. 1994 Nov;70(5):922–927. doi: 10.1038/bjc.1994.421

Cytogenetic analysis of multifocal breast carcinomas: detection of karyotypically unrelated clones as well as clonal similarities between tumour foci.

M R Teixeira 1, N Pandis 1, G Bardi 1, J A Andersen 1, N Mandahl 1, F Mitelman 1, S Heim 1
PMCID: PMC2033552  PMID: 7947098

Abstract

Cytogenetic analysis was performed on short-term cell cultures of two foci (A and B) from each of three multifocal breast carcinomas. In case I, four clones (three related and one unrelated) were detected in sample A. In sample B, two of the three related clones and the unrelated clone seen in A were found, as was also a third subclone showing a pattern of clonal evolution slightly different from that detected in A. In cases II and III, multiple cytogenetically unrelated clones were found in A and B, with only one clone being shared by both foci in each case. Our finding of cytogenetic similarities between macroscopically distinct tumour lesions indicates that the multifocality reflects intramammary tumour spread rather than the synchronous emergence of pathogenetically independent carcinomas within the same breast. On the other hand, the detection of karyotypic heterogeneity in the form of cytogenetically unrelated clones in all foci suggests that human breast carcinoma may be polyclonal. This polyclonality may be part of the explanation for the cellular heterogeneity commonly seen at the phenotypic level in breast cancer.

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Selected References

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  1. Bardi G., Johansson B., Pandis N., Mandahl N., Bak-Jensen E., Lindström C., Törnqvist A., Frederiksen H., Andrén-Sandberg A., Mitelman F. Cytogenetic analysis of 52 colorectal carcinomas--non-random aberration pattern and correlation with pathologic parameters. Int J Cancer. 1993 Sep 30;55(3):422–428. doi: 10.1002/ijc.2910550317. [DOI] [PubMed] [Google Scholar]
  2. Crissman J. D., Visscher D. W., Kubus J. Image cytophotometric DNA analysis of atypical hyperplasias and intraductal carcinomas of the breast. Arch Pathol Lab Med. 1990 Dec;114(12):1249–1253. [PubMed] [Google Scholar]
  3. Dawson P. J. What is new in our understanding of multifocal breast cancer. Pathol Res Pract. 1993 Feb;189(1):111–116. doi: 10.1016/S0344-0338(11)80130-5. [DOI] [PubMed] [Google Scholar]
  4. Devilee P., Cornelisse C. J. Genetics of human breast cancer. Cancer Surv. 1990;9(4):605–630. [PubMed] [Google Scholar]
  5. Dutrillaux B., Gerbault-Seureau M., Zafrani B. Characterization of chromosomal anomalies in human breast cancer. A comparison of 30 paradiploid cases with few chromosome changes. Cancer Genet Cytogenet. 1990 Oct 15;49(2):203–217. doi: 10.1016/0165-4608(90)90143-x. [DOI] [PubMed] [Google Scholar]
  6. Fuhr J. E., Frye A., Kattine A. A., Van Meter S. Flow cytometric determination of breast tumor heterogeneity. Cancer. 1991 Mar 1;67(5):1401–1405. doi: 10.1002/1097-0142(19910301)67:5<1401::aid-cncr2820670521>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  7. Geleick D., Müller H., Matter A., Torhorst J., Regenass U. Cytogenetics of breast cancer. Cancer Genet Cytogenet. 1990 Jun;46(2):217–229. doi: 10.1016/0165-4608(90)90107-l. [DOI] [PubMed] [Google Scholar]
  8. Gerbault-Seureau M., Vielh P., Zafrani B., Salmon R., Dutrillaux B. Cytogenetic study of twelve human near-diploid breast cancers with chromosomal changes. Ann Genet. 1987;30(3):138–145. [PubMed] [Google Scholar]
  9. Harris J. R., Lippman M. E., Veronesi U., Willett W. Breast cancer (1) N Engl J Med. 1992 Jul 30;327(5):319–328. doi: 10.1056/NEJM199207303270505. [DOI] [PubMed] [Google Scholar]
  10. Heim S., Caron M., Jin Y., Mandahl N., Mitelman F. Genetic convergence during serial in vitro passage of a polyclonal squamous cell carcinoma. Cytogenet Cell Genet. 1989;52(3-4):133–135. doi: 10.1159/000132862. [DOI] [PubMed] [Google Scholar]
  11. Heim S., Mandahl N., Mitelman F. Genetic convergence and divergence in tumor progression. Cancer Res. 1988 Nov 1;48(21):5911–5916. [PubMed] [Google Scholar]
  12. Heim S., Mertens F., Jin Y. S., Mandahl N., Johansson B., Biörklund A., Wennerberg J., Jonsson N., Mitelman F. Diverse chromosome abnormalities in squamous cell carcinomas of the skin. Cancer Genet Cytogenet. 1989 May;39(1):69–76. doi: 10.1016/0165-4608(89)90231-8. [DOI] [PubMed] [Google Scholar]
  13. Heppner G. H. Tumor heterogeneity. Cancer Res. 1984 Jun;44(6):2259–2265. [PubMed] [Google Scholar]
  14. Holland R., Veling S. H., Mravunac M., Hendriks J. H. Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery. Cancer. 1985 Sep 1;56(5):979–990. doi: 10.1002/1097-0142(19850901)56:5<979::aid-cncr2820560502>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  15. Jin Y. S., Heim S., Mandahl N., Biörklund A., Wennerberg J., Mitelman F. Unrelated clonal chromosomal aberrations in carcinomas of the oral cavity. Genes Chromosomes Cancer. 1990 Jan;1(3):209–215. doi: 10.1002/gcc.2870010304. [DOI] [PubMed] [Google Scholar]
  16. Kallioniemi O. P. Comparison of fresh and paraffin-embedded tissue as starting material for DNA flow cytometry and evaluation of intratumor heterogeneity. Cytometry. 1988 Mar;9(2):164–169. doi: 10.1002/cyto.990090211. [DOI] [PubMed] [Google Scholar]
  17. Noguchi S., Motomura K., Inaji H., Imaoka S., Koyama H. Clonal analysis of human breast cancer by means of the polymerase chain reaction. Cancer Res. 1992 Dec 1;52(23):6594–6597. [PubMed] [Google Scholar]
  18. Nowell P. C. Mechanisms of tumor progression. Cancer Res. 1986 May;46(5):2203–2207. [PubMed] [Google Scholar]
  19. Orndal C., Mandahl N., Willén H., Rydholm A., Mitelman F. Cytogenetic evolution in primary tumors, local recurrences, and pulmonary metastases of two soft tissue sarcomas. Clin Exp Metastasis. 1993 Sep;11(5):401–408. doi: 10.1007/BF00132983. [DOI] [PubMed] [Google Scholar]
  20. Pandis N., Heim S., Bardi G., Idvall I., Mandahl N., Mitelman F. Chromosome analysis of 20 breast carcinomas: cytogenetic multiclonality and karyotypic-pathologic correlations. Genes Chromosomes Cancer. 1993 Jan;6(1):51–57. doi: 10.1002/gcc.2870060110. [DOI] [PubMed] [Google Scholar]
  21. Pandis N., Heim S., Bardi G., Idvall I., Mandahl N., Mitelman F. Whole-arm t(1;16) and i(1q) as sole anomalies identify gain of 1q as a primary chromosomal abnormality in breast cancer. Genes Chromosomes Cancer. 1992 Oct;5(3):235–238. doi: 10.1002/gcc.2870050310. [DOI] [PubMed] [Google Scholar]
  22. Pandis N., Heim S., Bardi G., Limon J., Mandahl N., Mitelman F. Improved technique for short-term culture and cytogenetic analysis of human breast cancer. Genes Chromosomes Cancer. 1992 Jul;5(1):14–20. doi: 10.1002/gcc.2870050103. [DOI] [PubMed] [Google Scholar]
  23. Pandis N., Jin Y., Limon J., Bardi G., Idvall I., Mandahl N., Mitelman F., Heim S. Interstitial deletion of the short arm of chromosome 3 as a primary chromosome abnormality in carcinomas of the breast. Genes Chromosomes Cancer. 1993 Mar;6(3):151–155. doi: 10.1002/gcc.2870060304. [DOI] [PubMed] [Google Scholar]
  24. Petersen O. W., van Deurs B. Preservation of defined phenotypic traits in short-term cultured human breast carcinoma derived epithelial cells. Cancer Res. 1987 Feb 1;47(3):856–866. [PubMed] [Google Scholar]
  25. Saint-Ruf C., Gerbault-Seureau M., Viegas-Péquignot E., Zafrani B., Cassingena R., Dutrillaux B. Proto-oncogene amplification and homogeneously staining regions in human breast carcinomas. Genes Chromosomes Cancer. 1990 May;2(1):18–26. doi: 10.1002/gcc.2870020105. [DOI] [PubMed] [Google Scholar]
  26. Schmidt-Ullrich R., Lin P. S., Mikkelsen R. B., Monroe M. M. Proliferative rates of cloned malignant mammary epithelial cells as a measure of clonal heterogeneity in human breast carcinomas. J Natl Cancer Inst. 1986 Nov;77(5):1001–1011. [PubMed] [Google Scholar]
  27. Thompson F., Emerson J., Dalton W., Yang J. M., McGee D., Villar H., Knox S., Massey K., Weinstein R., Bhattacharyya A. Clonal chromosome abnormalities in human breast carcinomas. I. Twenty-eight cases with primary disease. Genes Chromosomes Cancer. 1993 Aug;7(4):185–193. doi: 10.1002/gcc.2870070402. [DOI] [PubMed] [Google Scholar]
  28. Wainscoat J. S., Fey M. F. Assessment of clonality in human tumors: a review. Cancer Res. 1990 Mar 1;50(5):1355–1360. [PubMed] [Google Scholar]
  29. Wolman S. R., Heppner G. H. Genetic heterogeneity in breast cancer. J Natl Cancer Inst. 1992 Apr 1;84(7):469–470. doi: 10.1093/jnci/84.7.469. [DOI] [PubMed] [Google Scholar]

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