Molecular characterization of the t(3;9) associated with immortalization in the MCF10A cell line

John Kenneth Cowell, Jeffrey LaDuca, Michael R. Rossi, Tania Burkhardt, Norma J. Nowak, Sei Ichi Matsui

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

The t(3;9)(p14;p21) in the MCF10A human mammary gland epithelial cell line was the single cytogenetic event that accompanied the transition from primary culture to immortalized cell line, suggesting that it is related to the development of the immortalization phenotype. To study the molecular consequences of the breakpoints in this rearrangement, we used a combination of fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (CGH). The 3p14 translocation breakpoint occurs within BAC RP11-795e22, which accommodates only the TAFA1 gene, a novel cysteine-rich secreted protein thought to be involved in cytokine signaling. TAFA1 is expressed in normal breast tissue, not in MCF10A, and shows differential expression in a range of breast cancer cell lines. The 9p translocation breakpoint results in a deletion of approximately 4 megabases on the derivative chromosome 9, which includes the CDKN2A (p16) gene. Array CGH and FISH analysis demonstrated that BAC 149i22, which contains the CDKN2A/B genes, is also deleted specifically on the apparently normal copy of chromosome 9, making MCF10A null for the p16/p15 genes. The exact extent of gains and losses of chromosome regions resulting from rearrangements involving chromosomes 1q, 5q, and 8q have also been characterized using the BAC arrays.

Original languageEnglish (US)
Pages (from-to)23-29
Number of pages7
JournalCancer Genetics and Cytogenetics
Volume163
Issue number1
DOIs
StatePublished - Nov 1 2005

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p16 Genes
Cell Line
Chromosomes, Human, Pair 9
Comparative Genomic Hybridization
Fluorescence In Situ Hybridization
Chromosomes
Human Mammary Glands
Cytogenetics
In Situ Hybridization
Cysteine
Breast
Epithelial Cells
Breast Neoplasms
Cytokines
Phenotype
Genes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Molecular characterization of the t(3;9) associated with immortalization in the MCF10A cell line. / Cowell, John Kenneth; LaDuca, Jeffrey; Rossi, Michael R.; Burkhardt, Tania; Nowak, Norma J.; Matsui, Sei Ichi.

In: Cancer Genetics and Cytogenetics, Vol. 163, No. 1, 01.11.2005, p. 23-29.

Research output: Contribution to journalArticle

Cowell, John Kenneth ; LaDuca, Jeffrey ; Rossi, Michael R. ; Burkhardt, Tania ; Nowak, Norma J. ; Matsui, Sei Ichi. / Molecular characterization of the t(3;9) associated with immortalization in the MCF10A cell line. In: Cancer Genetics and Cytogenetics. 2005 ; Vol. 163, No. 1. pp. 23-29.
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