Director's Note - July 2010

July 1, 2010, by Daniela S. Gerhard, Ph.D.

On July 13, 2010, President Barack Obama issued a letter on a National HIV/AIDS strategy. He wrote:

“Thirty years ago, the first cases of human immunodeficiency virus (HIV) garnered the world’s attention. Since then, over 575,000 Americans have lost their lives to AIDS and more than 56,000 people in the United States become infected with HIV each year. Currently, there are more than 1.1 million Americans living with HIV. Moreover, almost half of all Americans know someone living with HIV. Our country is at a crossroads. Right now, we are experiencing a domestic epidemic that demands a renewed commitment, increased public attention, and leadership.”

With an increase in the number of Americans affected by AIDS and their associated risk for certain types of cancers, the National Cancer Institute (NCI) Office of Cancer Genomics (OCG) and the NCI Office of HIV and AIDS Malignancies initiated the HIV+ Tumor Molecular Characterization Project (H+TMCP) with the goal of understanding the effect of HIV-infection on the development of certain cancers.

The advent of highly active anti-retroviral therapy (HAART) has considerably slowed disease progression from HIV to full-blown AIDS, thereby increasing the number of people living with HIV. It is not known why the incidence of certain cancers, but not others, increases in patients with HIV infection. Among the cancers with elevated prevalence is aggressive B-cell Non-Hodgkin lymphoma (NHL) and late-stage lung cancer. Even though some cancers have a viral origin, and immunodeficiency could more readily lead to the development of tumors caused by viruses, many questions remain.

Opportunity:

Second- and third-generation sequencing technologies and informatics tools allow nearly complete characterization of tumor transcriptomes and tumor genomes, together with identification of sequence alterations. Initial results support the concept that many of the chromosome, transcriptome and epigenome changes in cancer cells are not directly related to cancer development. Therefore, different analytical and experimental approaches need to be used to distinguish between “driver” and “passenger” alterations, including the characterization of similar tumors that arise in the context of the complex biological setting.

NCI already supports tumor genome characterization initiatives for both NHL and lung malignancies occurring in individuals with competent immune systems (immunocompetent) through the Cancer Genome Characterization Initiative and The Cancer Genome Atlas program. Therefore, by using systems biology analytical methods in H+TMCP to compare cancers with identical histologic subtypes that develop in both immunocompetent and immunodeficient people, we should be able to identify the mechanisms that either:

• allow tumors to counteract one’s innate cancer immunity (immune surveillance), or
• become altered only in the presence of external cancer-causing factors, such as oncogenic viruses

Specifically, H+TMCP will identify the potentially causative mutations and their associated pathways occurring in HIV-associated cancers which may respond to new or existing treatments. H+TMCP is just one example of how OCG integrates various trans-NCI projects and empowers the research community with the goal of developing better treatments for patients with cancer. All data generated will be made available to the scientific community for further analysis and use.

Sincerely,

Daniela S. Gerhard, Ph.D.
Director, NCI Office of Cancer Genomics