Identifikation neuer rekurrenter Kopienzahlveränderungen bei der chronisch lymphatischen Leukämie mittels hochauflösendem Einzelnukleotid-Polymorphismus-Array

Abstract

Chronic lymphocytic leukemia (CLL) is a disease with a heterogenous clinical course. Furthermore the pathogenesis of CLL is poorly understood. Recurrent genomic aberrations have a prognostic and therapeutic value although they can not predict all individual courses of this disease. We performed a SNP-Array analysis in 353 CLL-patients in order to detect unknown recurrent gemonic aberrations with clinical and/or pathogenetic impact. We detected a mean of 1,8 copy number alterations per case, 6% of all patients had copy-neutral loss-of-heterozygositv (CN-LOH). The most recurrent aberration detected was a gain in 8q24.21 which was detected in 16 cases (4,5%). Multivariate analysis identified a signicant reduced progression free survival (PFS). The second most identified aberration was a deletion in 15q15.1. Tumorspecific CN-LOH were detected in 20 cases and were associated with focal biallelic deletions. Gene sequencing analysis of the genes RPA2 and ATRIP showed no genomic alteration. Sequencing of MGA was performed in 59 cases and showed a non-sense mutation (C à T) in one case. After first-line-treatment and CLL-relapse 9 months later this aberration was not detectable anymore. Our investigations indicate a comparatively high genomic stability in CLL in comparison to other hematological diseases. Reduced progression free survival in cases with gain(8q24.21) does not go in line with previsous studies which reported a reduced overall survival. Further studies are needed to confirm the recurrency of MGA-mutations in CLL and prove a potential tumorsuppressive function of MGA in this disease.