By Mario Marcondes, MD, and Bart Scott, MD

2008-12-06

In this morning’s Scientific Committee session on Genomics and Epigenomics in Myeloid Malignancies, the lights will be focused on new technologies that will play an integral part in cancer therapy and also cancer fingerprinting in the future.

Dr. Ari M. Melnick, from Weill Cornell Medical College, NY, will discuss the relevance of epigenomics in regard to malignant transformation. Overall, the emerging field of epigenomics could provide a new opportunity for accurately identifying biological variation and therapeutically targeting myeloid malignancies. Dr. Melnick will discuss molecular aspects of genetic lesions that could affect cancer-related genes, such as CDKN2B, CDKN2A, RB, and BRCA1, and possible epigenetic deregulation that could form a part of the multi-step process of oncogenesis.

Following Dr. Melnick’s presentation, Dr. Timothy J. Ley will address the current uses of next-generation technologies using genomic DNA of tumor cells and normal tissue counterparts from the same donor. Whole genome sequencing has been impractical due to costs of conventional capillary-based sequencing and the requirement of large numbers of primary tumor cells required to yield the necessary genomic DNA for library preparation. The next-generation-sequencing-technique approaches have changed the landscape dramatically and should shed some light on the mechanism of oncologic disease, which is markedly heterogeneous. It remains to be seen if cancer stem cells differ in their genomics from their daughter tumor cells. Nevertheless, it is clear that the emerging patterns of abnormalities may yield future targets of molecular therapies, and individualized profiling of a particular patient’s cancer will allow clinicians to select and combine molecularly targeted therapies rationally.

Finally, Dr. James R. Downing will discuss differences in the spectrum of genetic lesions in myeloid and lymphoid malignancies. Recent breakthroughs in genomic technology have allowed researchers to perform a global analysis of malignancies on a genomic basis in order to determine changes in gene dosage and subsequent alterations in meaningful biologic pathways that could account for the underlying disease and possible relapse. Somatic copy number abnormalities (CNA) per cases/patients could show a lower frequency of recurrent lesions and a higher frequency of patients lacking any CNA. A wide range of genetic alterations contribute to the formation of leukemia. Collectively, these data could demonstrate differences in the spectrum of genetic lesions in myeloid and lymphoid malignancies. These qualitative data could suggest fundamental differences in the type of collaborating mutations between myeloid and lymphoid malignancies.

The field of genomics and epigenomics continues to advance our knowledge in oncogenesis and offer exciting new therapeutic pathways for the treatment of all malignancies. We look forward to ongoing discussions in the scientific community regarding this emerging field.

Drs. Marcondes and Scott indicated no relevant conflicts of interest.

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