Title | Gene dysregulations driven by somatic copy number aberrations-biological and clinical implications in colon tumors: a paper from the 2009 William Beaumont Hospital Symposium on Molecular Pathology. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Bacolod MD, Barany F |
Journal | J Mol Diagn |
Volume | 12 |
Issue | 5 |
Pagination | 552-61 |
Date Published | 2010 Sep |
ISSN | 1943-7811 |
Keywords | Chromosome Aberrations, Colonic Neoplasms, Disease Progression, Gene Dosage, Humans |
Abstract | The majority of colorectal cancer (CRC) cases have chromosomal instability, in which the tumor genome is characterized by gross chromosomal aberrations such as gains in 20q, 13q, 8q, and 7, and losses in 4, 8p, 18q, and 17p. These somatic copy number changes (gains, losses, and somatic uniparental disomies) are crucial to CRC progression as they drive genes toward cancer-promoting (oncogenic or tumor suppressive) states. Numerous studies have shown that the loss of 18q or 8p is associated with poorer clinical outcome in CRCs. Either chromosomal arm may contain a tumor suppressor gene (or genes), whose deactivation by copy loss (loss of wild-type allele, decreased expression) can be crucial to the later stages of cancer progression. Our own integrated genomic analysis (single nucleotide polymorphism array, expression array) of more than 200 CRC tumor and normal samples indicates that the overall down-regulation of genes within the 8p or 18q arm is associated with lower survival rate. Among the often down-regulated, poor prognosis-associated 8p genes is MTUS1, whose gene product (a mitotic spindle-associated protein) was recently demonstrated to have a tumor suppressive property. Within 18q is ATP5A1, which codes for the catalytic a component of mitochondrial H(+)-ATP synthase. Like SMAD4 (also in 18q), the decreased expression of ATP5A1 appears to be a marker of unfavorable clinical outcome in CRCs. |
DOI | 10.2353/jmoldx.2010.100098 |
Alternate Journal | J Mol Diagn |
PubMed ID | 20709793 |
PubMed Central ID | PMC2928418 |
Grant List | 263MQ610681 / / PHS HHS / United States P01-CA65930 / CA / NCI NIH HHS / United States |
Submitted by mam2155 on March 24, 2014 - 4:10pm