Protein Amplification In Melanoma Is Possible Drug Target

Gene amplification is a process that often happens in cancer cells when the normal DNA replication process is altered, causing many copies of the gene to be produced instead of a single copy of a region of a chromosome.

The researchers found that the MITF (microphthalmia-associated transcription factor) master regulator is the target of gene amplification in melanoma. MITF amplification also was more prevalent in metastatic disease and was correlated with decreased overall patient survival.

Collaborators at Yale, using the technology AQUA (Automated Quantitative Analysis) to quantitatively measure protein expression in melanoma tissue microarrays, also found an over-expression of the protein.

"According to the study, these data suggest that MITF represents a distinct class of 'lineage survival' or 'lineage addiction' oncogenes required for both tissue-specific development and tumor progression," said David Rimm, M.D., an author on the study and associate professor in the Department of Pathology at Yale School of Medicine.

Another Yale author on the study was Aaron Berger, a student in Rimm's laboratory. The corresponding author was William Sellers of Dana-Farber Cancer Institute in Boston. Co-authors included researchers at Brigham and Women's Hospital, Harvard, the Massachusetts Institute of Technology, Massachusetts General Hospital, and the Medical University of Vienna.

The AQUA technology is the property of HistoRx, Inc., a New Haven-based bioscience company offering novel digital technologies for in situ diagnostics developed at Yale School of Medicine. It enables researchers to localize and quantify proteins in tissue while maintaining spatial relationships--a process that was previously impossible with conventional methods of pathology analysis and which vastly increases the quality and amount of information for analysis.

Nature 436: 117-122 (July 7, 2005)