Vergleichende genomische Hybridisierung (CGH) zur Aufklärung genomischer Imbalancen bei hämatologischen Neoplasien mit Chromosomensätzen über 50 Elemente

We used comparative genomic hybridization to study the chromosomal status of 20 adult patients with haematological malignancies (16 ALL, 2 AML and 2 NHL). In 8 cases CGH was performed with DNA recovered from fixed cells by the use of chelating resins and universally amplified by DOP-PCR. The results did not differ from those performed with conventionally prepared DNA if normal genomic DNA that had also undergone DOP-PCR was used as reference sample. The childhood ALL > 50 chromosomes is associated with a favorable prognosis. No such favorable prognosis can be identified in adult ALL > 50. A certain pattern of chromosome gains und losses has been described in ALL > 50. In this study the hyperdiploid cases did have the same distribution of gained chromosomes as described in childhood ALL (4, 6, 10, 14, 17, 18, 21, X). So the difference in prognosis may be not explained by a different chromosome pattern. Structural chromosomal abnormalities in general are associated with a poor treatment outcome. The combination of CGH und conventional karyotyping provides more precise information about structural chromosomal abnormalities than conventional cytogenetics alone. In the combined analysis we found that the amount of structural chromosomal abnormalities in our adult patients with ALL > 50 was higher than the amount described in children. This result may explain the difference in treatment outcome between children and adults with ALL > 50. The CGH revealed losses at 9p which were not detected by cytogenetic analysis. At 2q21q31, 3q24q26 and 13q21q32 partial gains were detected, possibly nonrandom abnormalities in adult ALL > 50. In a case with tetraploid karyotype CGH found an isochromosome 17q, that possibly indicates the formation of the tetraploid karyotype by loss of tumor suppressor gene TP53 and following duplication of the karyotype. In the two cases of NHL CGH found gains of chromosomal material on 1q, 3q, 8q, 13q and 18q and losses of 17q, imbalances that are known to be associated with tumor progression and clinical outcome. At Xq28 CGH detected a gain of chromosomal material in a region where a lymphoma-associated oncogene may exist. In one case of tetraploid AML CGH revealed an isochromosome 8q and loss of 5q, both are markers of secondary acute myeloid leukemia.