TGen-led team is 1 of 7 selected for $1 million skin-cancer grants

Aug. 1, 2009 - An international scientific team led by the Translational Genomics Research Institute (TGen) has received a $1 million grant to study skin cancer from the Melanoma Research Alliance.

The grant was made to a team led by Dr. Jeffrey Trent, TGen's President and Research Director, who is the Team Lead among the Principal Investigators in the two-year study: Identification of Novel Melanoma Risk Genes Using High-throughput Genomics.

"The world-wide team of investigators on this project has worked together for a decade to identify individuals and families who are at increased risk for this deadly disease. While the team includes investigators from Europe and Australia, the research is particularly important to Arizonans who are disproportionately affected,'' Dr. Trent said.

Dr. Kevin Brown, an Associate Investigator in TGen's Integrated Cancer Genomics Division, also described the TGen-led team as part of an ongoing collaboration with the International Melanoma Genetics Consortium (GenoMEL), which has identified families worldwide that are predisposed to getting skin cancer.

"There are situations in which there is a strong family history of melanoma. If you can identify the genes, or mutations, that put people at risk for melanoma, you can implement targeted screening or prevention efforts,'' Dr. Brown said.

"Identifying the genes that mediate development of melanoma will give you an understanding of the basic biology, and conceivably could give you some clues into ways that you could do chemo prevention, or other things, for people who are at strong risk of getting melanoma,'' Dr. Brown said.

The other Principal Investigators in the TGen-led research are: Dr. Nicolas Hayward of the Queensland (Australia) Institute of Medical Research; Dr. Goran Jonsson of Lund (Sweden) University; and Dr. Graham Mann of the University of Sydney (Australia).

Arizona's non-Hispanic Caucasian population has among the nation's highest incidence rate of skin cancer. Australia has the highest incidence rate of the disease in the world.

The TGen-led team was one of seven multidisciplinary groups who received a total of $6.9 million in awards June 30 from the Washington, D.C.-based Melanoma Research Alliance (MRA) to pursue novel, outcomes-driven melanoma research.

These awards are part of the MRA's second round of grants focused on research that addresses gaps in translational science. In its second year of grant-making, MRA is now supporting 37 of the most promising melanoma research programs worldwide, totaling more than $16 million (including $6.9 million awarded July 30) in an effort to accelerate progress toward a cure.

"We are energized by the quality of proposals we continue to receive from the melanoma research community. In this latest round of grants, we are pleased to support seven multidisciplinary approaches that hold great potential to advance melanoma treatments," said Dr. Suzanne Topalian, M.D., Chair of the MRA Grant Review Committee and Director of the Johns Hopkins Melanoma Program.

According to the grant description presented by Dr. Trent:

"Early detection of cutaneous malignant melanoma offers the best form of cure. Characterization of the genes influencing melanoma risk is critical towards efforts aimed at disease prevention and early detection.

"Studies of families with multiple melanoma patients have identified mutations in two genes that strongly predispose to the disease, but these mutations are found only in a minority of families.

"To identify additional genes, the International Melanoma Genetics Consortium (GenoMEL) recently completed the largest genetic study of melanoma families to date, comprising 174 families with three or more melanoma patients. This study identified two chromosome positions likely to harbor melanoma susceptibility genes, while a separate smaller study by a GenoMEL member group has identified a third.

"We propose here to extend this collaborative effort by screening all genes at these three chromosomal locations for disease-predisposing mutations in melanoma families. We will also work towards identifying additional susceptibility genes by sequencing the entire genomes of patients from five of the largest melanoma families.

"The identification of novel predisposition genes is a major first step towards accurately estimating individualized disease risk and ultimately implementing disease prevention and early-detection strategies for at-risk individuals. Further, characterization of the molecular mechanisms underlying melanoma susceptibility may lead to a better understanding of the processes underlying melanoma development and progression, and ultimately to novel strategies for melanoma treatment."

The other teams receiving the latest round of MRA grants are:

Developing Melanoma Screening in Primary Care

Principal Investigators:

Team Lead: Martin A. Weinstock, M.D., Ph.D., Rhode Island Hospital and Brown University

Maryam Asgari, M.D., M.P.H., Kaiser Foundation Research Institute

Melody Eide, M.D., M.P.H., Henry Ford Health System

Suzanne Fletcher, M.D., M.Sc., Harvard Pilgrim Health Care and Harvard Medical School

Alan Geller, R.N., M.P.H., Harvard School of Public Health

Allan Halpern, M.D., M.S., Memorial Sloan-Kettering Cancer Center

Manipulating Immune Regulation in Adoptive T-cell Therapy for Melanoma Principal Investigators:

Team Lead: Jeffrey Weber, M.D., Ph.D., H. Lee Moffitt Cancer Center and Research Institute

Patrick Hwu, M.D., M.D. Anderson Cancer Center

Identification and Validation of Combination Therapies for Melanomas

Principal Investigators:

Team Lead: Michael J. Weber, Ph.D., University of Virginia

Levi Garraway, M.D., Ph.D., Dana-Farber Cancer Institute

Dan Gioeli, Ph.D., University of Virginia

Proposal Title: Sequencing of the Melanoma Exome, Transcriptome and Epigenome Principal Investigators:

Team Lead: Ruth Halaban, Ph.D., Yale University

Marcus Bosenberg, M.D., Ph.D., Yale University

Michael Krauthammer, M.D., Ph.D., Yale University

David Stern, Ph.D., Yale University

Combinatorial Immunotherapy for Melanoma with B7-H1/PD-1 Checkpoint Blockade

Principal Investigators:

Team Lead: Drew Pardoll, M.D., Ph.D., Johns Hopkins University

Lieping Chen, M.D., Ph.D., Johns Hopkins University

Suzanne Topalian, M.D., Johns Hopkins University

Identification of Novel Melanoma Risk Genes Using High-throughput Genomics Principal Investigators:

Team Lead: Jeffrey Trent, Ph.D., Translational Genomics Research Institute

Nicolas Hayward, Ph.D., Queensland Institute of Medical Research

Goran Jonsson, Ph.D., Lund University

Graham Mann, Ph.D., The University of Sydney

Defining the Importance of Immunity to NY-ESO-1 in Melanoma

(Co-funded by the Cancer Research Institute)

Principal Investigators:

Team Lead: Jedd D. Wolchok, M.D., Ph.D., Memorial Sloan-Kettering Cancer Center

James P. Allison, Ph.D., Memorial Sloan-Kettering Cancer Center

Jonathan Cebon, Ph.D., Ludwig Institute for Cancer Research

Alexander Eggermont, M.D., Ph.D., Daniel den Hoed Cancer Center

Sacha Gnjatic, Ph.D., Ludwig Institute for Cancer Research

Dirk Jäger, M.D., University Hospital Heidelberg

Elke Jäger, Ph.D., Goethe University Frankfurt

Alexander Knuth, M.D., University of Zurich

Lloyd J. Old, M.D., Ludwig Institute for Cancer Research

Source: The Translational Genomics Research Institute