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Genomics of childhood ALL disease susceptibility and treatment outcome

The Functional Human Variation group is hosting a talk by Doctor Jun J. Yang from the Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, USA.

Monday 1 July 2013 at 14:00
Center for Biological Sequence Analysis, auditorium 062 in building 208

Abstract: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and cure rates have improved dramatically thanks to progressive intensification and risk adapted chemotherapy. However, molecular etiology of ALL and genetic basis of inter-patient variability in treatment response are not fully understood. In recent genome-wide association studies (GWAS), we identified genomic loci that strongly influence the risk of developing ALL in children (Nat Genet 41:1001; J Natl Cancer Inst 105:733). Some of these variants contribute to racial differences in the incidence of ALL and are also related to age pattern of ALL. Taking a similar agnostic approach, our GWAS of treatment response phenotypes revealed germline genetic variants associated with minimal residual disease status at the end of induction therapy and subsequently those related to the risk of ALL relapse (JAMA 301:393; Nat Genet 43:237; Blood 120:4197). Focusing on tumor genomic lesions, we also identified genetic aberrations specific to relapsed ALL that were directly related to thiopurine resistance, through genomic profiling of matched diagnostic and relapse ALL blasts (Nat Genet 45:290; Blood 112:4178 and 118:5218). Together, these results shed exciting new light on molecular determinants of ALL pathogenesis and drug response, providing opportunities for the development of more individualized therapy to further improve the treatment outcome of childhood ALL.

Everybody is welcome. Registration is not necessary.