Introduction. In most types of adult cancer, aneuploidy leads to an unfavorable prognosis. In absence of segmental chromosomal alterations (SCA) infant neuroblastoma and low-risk tumors (INSS stage 1, 2, 4S) are frequently associated with hyperdiploidy or near-triploidy and have a clinical good prognosis. In pediatric acute lymphoblastic leukemia, hyperdiploidy is also associated with a good prognosis. The mechanisms leading to these types of genetic defects and associated good prognosis are poorly understood.
Methods. Array-CGH data from 96 neuroblastomas with only numerical chromosome alterations (NCA) were analyzed, using 68 cases from the R2 database (http://hgserver1.amc.nl/cgi-bin/r2/main.cgi) and 28 additional GHU cases.
Results. Analysis of the array-CGH confirmed a non-random pattern of whole chromosome gains and losses in NB with NCA only. The number of gains and losses was highly variable between the different tumors. In 14/96 tumors only chromosome gains were observed, 80/96 had a combination of gains and losses, in 2/96 tumors only loss of one chromosome was present. In tumors with gains (94/96), combination of chromosome 17 (n=87) and/or chromosome 6 and/or 7 gain was present in all cases (94/94). In 82/84 tumors with losses, these losses involved a combination of chromosome 14 (n=63), 11, 3, and 4. In tumors with gains and losses different combination patterns were seen. Chromosome 17 gain was accompanied by loss of 14 in 61/72 tumors, and with loss of chromosome 11/4/3 in 8/9 of the remaining cases. The 7 tumors without chromosome 17 gain always presented with a chromosome 6 or 7 gain and loss of chromosome 14.
Conclusion. In NB with NCA we found a typical pattern of combinations of gains of chromosomes 6/7/17 and losses of 3/4/11/14. As previously described, the typical segmental abnormalities present in tumors with SCAs involve the same chromosomes: 17q-gain, 3p/4p/11q/14q-deletions. Understanding the underlying pathophysiology requires further studies.