Chromosome 8 BAC array comparative genomic hybridization and expression analysis identify amplification and overexpression of TRMT12 in breast cancer

Virginia Rodriguez, Yidong Chen, Abdel Elkahloun, Amalia Dutra, Evgenia Pak, Settara Chandrasekharappa

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

Genomic changes in chromosome 8 are commonly observed in breast cancer cell lines and tumors. To fine map such genomic changes by comparative genomic hybridization (CGH), a high resolution (100 kb) chromosome 8 array that can detect single copy changes was developed using Phi29 DNA polymerase amplified BAC (bacterial artificial chromosome) DNA. The BAC array CGH resolved the two known amplified regions (8q21 and 8q24) of a breast cancer cell line (SKBR3) into nine separate regions including six amplicons and three deleted regions, all of which were verified by Fluorescence in situ hybridization. The extent of the gain/loss for each region was validated by qPCR. CGH was performed with a total of 8 breast cancer cell lines, and common regions of genomic amplification/deletion were identified by segmentation analysis. A 1.2-Mb region (125.3-126.5 Mb) and a 1.0-Mb region (128.1-129.1 Mb) in 8q24 were amplified in 7/8 cell lines. A global expression analysis was performed to evaluate expression changes associated with genomic amplification/deletion: a novel gene, TRMT12 (at 125.5 Mb), amplified in 7/8 cell lines, showed highest expression in these cell lines. Further analysis by RT-qPCR using RNA from 30 breast tumors showed that TRMT12 was overexpressed >2 fold in 87% (26/30) of the tumors. TRMT12 is a homologue of a yeast gene encoding a tRNA methyltransferase involved in the posttranscriptional modification of tRNAPhe, and exploring the biological consequence of its altered expression, may reveal novel pathways in tumorigenesis.

Original languageEnglish (US)
Pages (from-to)694-707
Number of pages14
JournalGenes Chromosomes and Cancer
Volume46
Issue number7
DOIs
StatePublished - Jul 2007
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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