Abstract
It has been hypothesized and subsequently shown that tumors arise as a result of an acquired genomic instability and the subsequent evolution of clonal populations of neoplastic cells. Thus the pattern and behavior of distinct genomically aberrant clones may underlie multiple clinical phenotypes in a variety of cancers. A fundamental hypothesis of cancer genome studies is that genes and cellular networks targeted by selected aberrations represent vulnerabilities that can be exploited for effective personalized therapies. However, the heterogeneity of neoplastic cells and the presence of admixtures of genomically normal cells make it difficult to comprehensively define cancer genomes in patients in vivo. By applying single parameter and multi parameter DNA content based flow cytometry of nuclei to isolate clonal populations from solid tumor biopsies, and coupling this strategy with array CGH, we obtained high definition genomic profiles of clonal populations from pancreatic adenocarcinomas (PA), adrenal cortical carcinomas (ACC), and prostate carcinomas (PC). The genomes of clonal populations in these disparate cancers have distinct patient‐specific sets of aberrations with clinical relevance. For example, our clonal analyses detected unique gene‐specific homozygous deletions converging on NOTCH signaling and multiple focal amplicons that target cell migration in PA, distinguished divergent clones within single biopsies, and identified genomic aberrations specific to therapeutically sensitive and resistant clones arising during the evolution of androgen independent metastatic PC. Application of these technologies in combination with next generation sequencing allows for elucidation of the unique clonal identities of cancer genomes in patients in vivo, which in turn can help guide diagnoses and tailor approaches to treatment.
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A206.
- Copyright © 2009, American Association for Cancer Research
Volume 8, Issue 12 Supplement
