collins@cc.ucsf.edu
(415) 502-7066 (lab); (415) 476-8218 (fax)

Box 0808, UCSF; San Francisco, CA 94143-0808

deliveries: 2340 Sutter Street, S-151; San Francisco, CA 94115

Full Biosketch

Adam Hittelman, MD; GuiQing Huang, MD, PhD; Pamela Paris, PhD; Shivaranjani Sridharan; Stas Volik, PhD

The prototypic example of oncogenomics research carried out in my laboratory is best exemplified by our work on a chromosome 20q13.2 breast cancer amplicon. This locus is amplified in approximately 20 percent of breast cancers. In breast tumors high level amplification is associated with high histologic grade, aneuploidy, high S-phase fraction, and short disease-free survival. It was hypothesized that amplification of a specific gene or genes within this amplicon leads to aberrant gene expression that is selected for as the tumor evolves toward a more aggressive phenotype. To identify the involved gene(s) we cloned and sequenced 1.2 Mb of DNA spanning the locus (Collins et al., 1998; Collins et al., 2001) and developed unique software for comprehensive biological annotation of the sequence (Collins et al, 2001). The ZNF217 gene was identified in the amplicon core and shown to immortalize cultured human mammary epithelial cells (Collins et al, 1998; Nonet et al, 2001). cDNA microarrays and yeast two-hybrid studies now suggest a mechanism for ZNF217 mediated immortalization, and this in turn suggests possible therapeutic strategies and targets.

Prostate cancer is diagnosed in approximately 200,000 men per year and kills 40,000 per year. I am principal investigator for project II on the UCSF Prostate Cancer SPORE (National Cancer Institute-sponsored Specialized Program Of Research Excellence). My laboratory is employing high-resolution array CGH to identify prognostic markers for stratification of patients with intermediate grade tumors into lower and higher risk groups to guide selection of appropriate therapy options. This will involve copy number profiling of 100 primary tumors by array CGH and marker validation on 800 primary tumors using tissue array technology. This work is performed in partnership with the informatics and clinical cores to ensure that new makers are delivered to clinical oncologists. In addition, we apply genome sequence analysis and functional genomics to identify new cancer genes implicated in tumor progression with the goal of developing therapeutics that can block progression. Two regions of intense interest map to chromosomes 16q22 and 16q24, respectively. Both loci are deleted in approximately 50 percent of prostate tumors. In prostate tumors, mutations in tumor suppressor genes are found less frequently than expected, suggesting that epigenetic events may silence the non-deleted allele. To investigate this hypothesis we are exploring various technologies for detecting aberrant methylation in prostate tumors. Finally, we are developing software for integration of cDNA microarray data with array CGH data. This integration should reduce the complexity of data analysis while identifying causal genetic events driving tumor progression and response to therapy.

In addition to breast and prostate cancer, my laboratory collaborates on projects directed at human ovarian and brain cancer, as well as mouse models of cancer.