Common pattern of unusual chromosome abnormalities in hereditary papillary renal carcinoma

Abstract

In this study, we summarized cytogenetic and comparative genomic hybridization (CGH) results, mutation analysis of the MET gene, and immunohistochemistry results of tumors from three patients in the same family who were affected by hereditary papillary renal carcinoma (HPRC). All three patients showed germline mutations in the tyrosine kinase domain of the MET proto-oncogene, and developed bilateral and multiple papillary renal tumors. DNA mutation analysis showed an increased dosage of the mutant allele in six tumors from two patients but not in two tumors from the third patient. In addition to the recurrent chromosomal alterations found in papillary renal carcinomas, cytogenetic analyses revealed the presence of an identical chromosomal translocation, t(2;15)(q13;p11), in two different tumors from the same patient. Moreover, the same pattern of autosomal trisomies (+7, +12, +13, +17) was detected by CGH analysis in tumors from different siblings. Taking into account that the presence of an identical structural chromosomal aberration in two tumors and the gain of chromosome 13 are unusual chromosomal changes in this type of tumor, we can conclude that our results confirm those of other authors and suggest that the genetic predisposition to HPRC might predispose the acquisition of genomic alterations in specific chromosomes or chromosomal regions.