Chromosomal analysis of renal angiomyolipoma by comparative genomic hybridization: Evidence for clonal origin

Angiomyolipoma has long been considered a hamartomatous polyclonal prolifer ation. However, recent molecular analyses have indicated that these tumors may be clonal neoplasms rather than polyclonal proliferations. We investiga ted chromosomal imbalances in angiomyolipoma by comparative genomic hybridi zation. DNA was extracted from archival paraffin-embedded and frozen tissue s of 12 angiomyolipomas (10 usual variant, two epithelioid variant). The 10 angiomyolipomas of the usual variant included bilateral tumors from one tu berous sclerosis patient. Fluorescence ratio distributions from tumor hybri dizations were compared with those from control hybridizations to detect ch anges in DNA copy number with high sensitivity and specificity. We identifi ed 20 chromosomal imbalances in seven sporadic angiomyolipomas, including b oth tumors of the epithelioid variant. The remaining five tumors, including the two angiomyolipomas from a tuberous sclerosis patient, were devoid of chromosomal imbalances. Seventy-five percent of the imbalances were partial or whole chromosomal deletions involving disparate genomic regions, some o f which have previously been associated with tumors of adipose tissue and s mooth muscle tumors. Four angiomyolipomas of the usual variant shelved 5q d eletions with a common region of deletion spanning 5q33 to q34. In two tame rs, deletion on 5q was the sole abnormality. One epithelioid angiomyolipoma showed 5q gain encompassing the same region in addition to other alteratio ns. We concluded that (1) Chromosomal imbalances are common in renal angiom yolipomas; (2) Presence of clonal genomic alterations lends further support to the neoplastic pathogenesis of these tumors; (3) The 5q33-q34 region ma y contain a tumor suppressor gene significant in the histogenesis of some r enal angiomyolipomas. HUM PATHOL 30:295-299, Copyright (C) 1999 by W.B. Sau nders, Company.