Leukemia and precision medicine. Doctors must do genomic sequencing in cancer cells AND in normal cells. 5

Leukemia and precision medicine. Doctors must do genomic sequencing in cancer cells AND in normal cells. 5

Leukemia and precision medicine. Doctors must do genomic sequencing in cancer cells AND in normal cells. 5

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Genomic sequencing [NGS, WES] of tumors is now common. But why do you need to sequence both cancer tissue from biopsy or tumor resection AND normal patient’s cells (often from skin cells, fibroblasts)? A significant share of cancers is hereditary. NGS information may have significance for treatment and for others in the extended family. Leading pediatric cancer expert shares his wisdom. You do genomic next generation sequencing [NGS] of child leukemia cells. Dr. Anton Titov, MD. What is the substrate for the sequencing? Is it peripheral blood cells? Is it the bone marrow biopsy? Dr. Shai Izraeli, MD. This is a complicated question that I will divide into two parts. I gave you an example for Philadelphia-like or Philadelphia leukemias with BCR-ABL abnormalities. These genetic mutations (chromosomal translocations) are found in leukemic cells. it's very important to sequence the cancer cells itself. Dr. Anton Titov, MD. Do you have to enrich cells for next generation sequencing [NGS] of cancer? Dr. Shai Izraeli, MD. Yes. I may give later an incredible example of child cancer cure that we had in our center recently. That cure shows you also the importance of tumor gene sequencing. Something else is also becoming more and more important. We learn that genetics is more and more important for tumors in childhood and in adult cancer. Dr. Shai Izraeli, MD. We think that up to 15% percent of cancers in children have a hereditary component. This is important! Because you may need to give to caner patient a bone marrow transplant from a brother or sister. But they might also have cancer-predisposing mutation. more and more we now also sequence the germline. Germline means not the leukemia cells itself. In blood cancer we often sequence the cell from a skin. We sequence a skin cell from a fibroblast culture of the skin. It's very common to get skin biopsies for children. Because we insert central venous lines for treatment of cancer in children. Central venous lines are done under anesthesia. We believe that this is a pain-free hospital. we do everything under anesthesia. Then we also take a skin biopsy. more and more we do germline sequencing from skin. We discover hereditary cancers in a family. we sequence both tissues. We do sequencing of cancer leukemic cells from bone marrow. Dr. Shai Izraeli, MD. We also sequence normal cells from the germline. They usually come from skin fibroblasts. Dr. Anton Titov, MD. These are true examples of precision medicine! Yes.

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