Loss of heterozygosity as a predictor to map tumor... : Current Opinion in Oncology (original) (raw)

Cancer biology

Loss of heterozygosity as a predictor to map tumor suppressor genes in cancer: molecular basis of its occurrence

Thiagalingam, Sam PhD*†; Foy, Rebecca L. BS*; Cheng, Kuang-hung MS†; Lee, Hyunjoo J. BA*; Thiagalingam, Arunthathi PhD‡; Ponte, Jose F. PhD*

*Genetics & Molecular Medicine Programs and Pulmonary Center, Department of Medicine and † Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA; and ‡ Bayer Corporation, East Walpole, Massachusetts, USA.

Correspondence to Sam Thiagalingam, PhD, Genetics Program, Boston University School of Medicine, 715 Albany Street, E603, Boston, MA 02118, USA; e-mail: [email protected]

Abstract

High frequency of chromosomal deletions elicited as losses of heterozygosity is a hallmark of genomic instability in cancer. Functional losses of tumor suppressor genes caused by loss of heterozygosity at defined regions during clonal selection for growth advantage define the minimally lost regions as their likely locations on chromosomes. Loss of heterozygosity is elicited at the molecular or cytogenetic level as a deletion, a gene conversion, single or double homologous and nonhomologous mitotic recombinations, a translocation, chromosome breakage and loss, chromosomal fusion or telomeric end-to-end fusions, or whole chromosome loss with or without accompanying duplication of the retained chromosome. Because of the high level of specificity, loss of heterozygosity has recently become invaluable as a marker for diagnosis and prognosis of cancer. The molecular defects for the occurrence of loss of heterozygosity are derived from disabled caretaker genes, which protect the integrity of DNA, or chromosome segregator genes, which mediate faithful chromosome disjunction.