Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis

Jennelle C. Hodge, Peter J. Park, Jonathan M. Dreyfuss, Iman Assil-Kishawi, Priya Somasundaram, Luwam G. Semere, Bradley J. Quade, Allison M. Lynch, Elizabeth A Stewart, Cynthia C. Morton

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including interstitial deletion of 7q. To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t tests demonstrates this matched design is critical to eliminate the confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome-wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1. Combining the aCGH data with the del(7q) UL mosaicism-weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity-maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis.

Original languageEnglish (US)
Pages (from-to)865-885
Number of pages21
JournalGenes Chromosomes and Cancer
Volume48
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

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Leiomyoma
Neoplasms
Genes
Tumor Suppressor Proteins
Karyotyping
Mosaicism
Ubiquitination
Oncogene Proteins
Mitosis
Gene Frequency
Chromosome Aberrations
Genotype
Maintenance
Genome
Breast Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Hodge, J. C., Park, P. J., Dreyfuss, J. M., Assil-Kishawi, I., Somasundaram, P., Semere, L. G., ... Morton, C. C. (2009). Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis. Genes Chromosomes and Cancer, 48(10), 865-885. https://doi.org/10.1002/gcc.20692

Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis. / Hodge, Jennelle C.; Park, Peter J.; Dreyfuss, Jonathan M.; Assil-Kishawi, Iman; Somasundaram, Priya; Semere, Luwam G.; Quade, Bradley J.; Lynch, Allison M.; Stewart, Elizabeth A; Morton, Cynthia C.

In: Genes Chromosomes and Cancer, Vol. 48, No. 10, 10.2009, p. 865-885.

Research output: Contribution to journalArticle

Hodge, JC, Park, PJ, Dreyfuss, JM, Assil-Kishawi, I, Somasundaram, P, Semere, LG, Quade, BJ, Lynch, AM, Stewart, EA & Morton, CC 2009, 'Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis', Genes Chromosomes and Cancer, vol. 48, no. 10, pp. 865-885. https://doi.org/10.1002/gcc.20692
Hodge, Jennelle C. ; Park, Peter J. ; Dreyfuss, Jonathan M. ; Assil-Kishawi, Iman ; Somasundaram, Priya ; Semere, Luwam G. ; Quade, Bradley J. ; Lynch, Allison M. ; Stewart, Elizabeth A ; Morton, Cynthia C. / Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis. In: Genes Chromosomes and Cancer. 2009 ; Vol. 48, No. 10. pp. 865-885.
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