11q21.1-11q23.3 Is a site of intrinsic genomic instability triggered by irradiation.

ABSTRACT

The chromosome location, 11q21-23, is linked to loss of heterozygosity (LOH) in multiple tumors including those of breast, lung, and head and neck. To examine the process of LOH induction, the H292 cell line (human muco-epidermoid carcinoma) was irradiated or treated with anti-CD95 antibody, and individual clones isolated through two rounds of cloning. Regions of LOH were determined by screening a suite of eight polymorphic microsatellite markers covering 11p15-11q24 using fluorescent primers and genetic analyzer peak discrimination. LOH induction was observed extending through 11q21.1-11q23.3 in 6/49 of clones surviving 4 Gy and 8/50 after 8 Gy. Analysis of selected clones by Affymetrix 6.0 single nucleotide polymorphism (SNP) arrays confirmed the initial assessment indicating a consistent 27.3-27.7 Mbp deletion in multiple clones. The telomeric border of LOH mapped to a 1 Mbp region of elevated recombination. Whole genome analysis of SNP data indicated that site-restricted LOH also occurred across multiple additional genomic locations. These data indicate that 11q21.1-11q23.3, and potentially other regions of this cell line are sites of intrinsic cell-specific instability leading to LOH after irradiation. Such deletions may subsequently be propagated by genetic selection and clonal expansion.