The extended survival of HIV-positive (HIV+) patients as a result of advanced therapies leads to an increased incidence of disease-related malignancies. In collaboration with the NCI Office of HIV and AIDS Malignancy, projects were launched to explore the characteristics of HIV-related lymphoma, lung, and head and neck cancers.
Five head and neck cancer SPOREs conduct collaborative clinical studies to assess changes of functional immune markers in HIV+ and HIV-negative (HIV-) cancer patients. Investigators are also collecting specimens from HIV+ and HIV- individuals with premalignant lesions to explore the molecular difference in these two groups using genomic and epigenetic approaches.
One lymphoma SPORE focuses on discovery of new genes associated with risk for and outcome of HIV-associated Burkitt’s lymphoma. The project uses whole exome sequencing of paired normal and tumor tissue samples from a given patient. This allows subtraction of germline polymorphisms from the data to reveal much less frequent mutations that are specific to the tumor. They also include HIV- Burkitt’s patients as controls in order to identify genes uniquely related to HIV-related Burkitt’s lymphoma. Recent results from analysis of matched tumor and normal tissue samples from five Burkitt’s lymphoma patients, two of whom are HIV+, revealed an unexpectedly high number of novel tumor-specific mutations (246) that are currently being confirmed on second generation platforms.
Lung cancer SPOREs explore molecular differences between tumors of HIV+ lung cancer patients and matched HIV- lung cancer controls by performing high-throughput genome analyses. They investigate new genetic epidemiology markers associated with the development of lung cancer in HIV+ patients, and study the role of viral cofactors that characterize the increased risk of developing lung cancer in these patients.