Genetic aberrations in hypodiploid breast cancer: Frequent loss of chromosome 4 and amplification of cyclin D1 oncogene

Minna M. Tanner, Ritva A. Karhu, Nina N. Nupponen, Åke Borg, Bo Baldetorp, Tanja Pejovic, Mårten Fernö, Dick Killander, Jorma J. Isola

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Abstract

The evolution of somatic genetic aberrations in breast cancer has remained poorly understood. The most common chromosomal abnormality is hyperdiploidy, which is thought to arise via a transient hypodiploid state. However, hypodiploidy persists in 1 to 2% of breast tumors, which are characterized by a poor prognosis. We studied the genetic aberrations in 15 flow cytometrically hypodiploid breast cancers by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). Surprisingly, numerous copy number gains were detected in addition to the copy number losses. The number of gains per tumor was 4.3 ± 3.2 and that of losses was 4.5 ± 3.3 (mean ± SD), which is similar to that previously observed in hyperdiploid breast cancers. Gains at chromosomes or chromosomal regions at 11q13, 1q, 19, and 16p and losses of 2q, 4, 6q, 9p, 13, and 18 were most commonly observed. Compared with unselected breast carcinomas, hypodiploid tumors showed certain differences. Loss of chromosome 4 (53%) and gain of 11q13 (60%) were significantly more common in hypodiploid tumors. The gain at 11q13 was found by FISH to harbor amplification of the Cyclin D1 oncogene, which is therefore three to four times more common in hypodiploid than in unselected breast cancers (15 to 20%). Structural chromosomal aberrations (such as Cyclin D1 amplification) were present both in diploid and hypodiploid tumor cell populations, as assessed by FISH and CGH after flow cytometric sorting. Together these results indicate that hypodiploid tumors form a distinct genetic entity of invasive breast cancer, although they probably share a common genetic evolution pathway where structural chromosomal aberrations precede gross DNA ploidy changes.

Original languageEnglish (US)
Pages (from-to)191-199
Number of pages9
JournalAmerican Journal of Pathology
Volume153
Issue number1
StatePublished - Jul 1998
Externally publishedYes

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Chromosomes, Human, Pair 4
Cyclin D1
Oncogenes
Breast Neoplasms
Fluorescence In Situ Hybridization
Chromosome Aberrations
Polyploidy
Comparative Genomic Hybridization
Molecular Evolution
Neoplasms
Clonal Evolution
Ploidies
Diploidy
In Situ Hybridization
Chromosomes
DNA
Population

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Tanner, M. M., Karhu, R. A., Nupponen, N. N., Borg, Å., Baldetorp, B., Pejovic, T., ... Isola, J. J. (1998). Genetic aberrations in hypodiploid breast cancer: Frequent loss of chromosome 4 and amplification of cyclin D1 oncogene. American Journal of Pathology, 153(1), 191-199.

Genetic aberrations in hypodiploid breast cancer : Frequent loss of chromosome 4 and amplification of cyclin D1 oncogene. / Tanner, Minna M.; Karhu, Ritva A.; Nupponen, Nina N.; Borg, Åke; Baldetorp, Bo; Pejovic, Tanja; Fernö, Mårten; Killander, Dick; Isola, Jorma J.

In: American Journal of Pathology, Vol. 153, No. 1, 07.1998, p. 191-199.

Research output: Contribution to journalArticle

Tanner, MM, Karhu, RA, Nupponen, NN, Borg, Å, Baldetorp, B, Pejovic, T, Fernö, M, Killander, D & Isola, JJ 1998, 'Genetic aberrations in hypodiploid breast cancer: Frequent loss of chromosome 4 and amplification of cyclin D1 oncogene', American Journal of Pathology, vol. 153, no. 1, pp. 191-199.
Tanner, Minna M. ; Karhu, Ritva A. ; Nupponen, Nina N. ; Borg, Åke ; Baldetorp, Bo ; Pejovic, Tanja ; Fernö, Mårten ; Killander, Dick ; Isola, Jorma J. / Genetic aberrations in hypodiploid breast cancer : Frequent loss of chromosome 4 and amplification of cyclin D1 oncogene. In: American Journal of Pathology. 1998 ; Vol. 153, No. 1. pp. 191-199.
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