11q23 allelic loss is associated with regional lymph node metastasis in melanoma

Genetic alterations of the long arm of chromosome 11 have been implicated i n melanoma pathogenesis, and we recently identified two distinct regions of common allelic loss in chromosomal band 11q23, To establish the point in t ime of melanoma tumorigenesis at which these two putative tumor suppressor loci become relevant, we investigated allelic loss [loss of heterozygosity (LOH)] in both chromosomal regions in tumors of progressing patients, We an alyzed 102 tumor samples from 23 patients for whom at least two (10 patient s) or three (13 patients) tumor samples from different clinical progression steps (such as primary tumor and/or in-transit metastasis and/or regional lymph node metastasis and/or distant metastasis) were available, We detecte d no 11q23 LOH at any stage in 3 of 23 patients and detected LOH at all sta ges tested in 8 of 23 patients. In 8 of the remaining 12 (67%) patients wit h 11q23 LOH at some stage during tumor progression, we found this to occur first at regional lymph node metastasis, Two of these patients retained con stitutional heterozygosity in several in-transit metastases that developed up to 7 months after lymph node metastases that already had loss, We theref ore conclude that 11q23 LOH is associated with regional lymph node metastas is in melanoma, Finally, we detected an allele shift restricted to a histom orphologically distinct part of a primary melanoma and found that the same parental chromosome was affected by allelic loss in a subsequently occurrin g lymph node metastasis, These findings support our conclusion and give add itional evidence for the hypothesis of molecular heterogeneity of early tum or cell populations in melanoma,