This is a grant competitive renewal requesting funding to further study multiple myeloma (MM) in patients, entered into the Eastern Cooperative Oncology Group (ECOG) clinical trials E9486/E9487 and prospective patients seen at the Mayo Clinic, by molecular cytogenetic methods to attempt a molecular classification of the disease. This proposal hopes to classify MM at a molecular level into discrete groups of patients with unique biology and prognosis. We will also further study the role chromosome 13 plays in the pathogenesis of MM.
Specific Aims 1. Using interphase FISH in newly diagnosed MM patient samples we will perform a comprehensive analysis of molecular cytogenetic abnormalities, including: IgH translocations and their specific partners; IgL-lambda translocations; deletions of 17p13.1 (p53), 11q23 (ATM), 9p21 (p16/INK4), and 22q; and delta13. By these means, we hope to elucidate their clinical, prognostic and biological importance in MM. We will test for these abnormalities in MM patients entered into the ECOG Phase III clinical trial E9486 and associated correlative laboratory study E9487. 2. To delineate a minimally deleted region of chromosome 13 to identify area suggestive of tumor suppressor gene deletions. 3. To assess for clonal evolution and selection of delta13 containing cells in longitudinally obtained samples. 4. To establish the prognostic significance of delta13 in MM patients undergoing high-dose chemotherapy with stem cell support and contrast this to the effect of delta13 on survival in MM patients treated with conventional chemotherapy.
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