Objective: Paragangliomas (PGLs) of the head and neck are benign neoplasms derived from the autonomic nervous system. Familial PGLs have been associated with germline mutations in succinate dehydrogenase (SDH) genes, and occasionally in Von Hippel-Lindau (VHL) and RET. The aim of this study was to compare somatic DNA copy number changes in tumors of familial and sporadic origin.
Material and methods: Eight familial and 16 sporadic patients were analyzed for germline mutations and exon deletions in SDHB, SDHC, SDHD, VHL, and RET by direct sequencing and MLPA. Microarray CGH analysis was applied to map genome-wide somatic copy number changes.
Results: Fifteen cases carried a germline mutation in SDHB or SDHD, four of which not described before. Microarray CGH detected abnormalities in 10 of 18 cases, most frequently concerning deletions at 1p, 1q, and 11q, the sites where SDH are located. However, these deletions occurred in both SDH mutation-positive and SDH mutation-negative cases.
Conclusions: These data suggest that inactivating germline SDH mutations and somatic deletions of SDH genes as a "second hit" are involved in a subset, but not in all PGLs. Additional genes and mechanisms may need to be studied, especially in the group of sporadic PGL showing no chromosomal aberrations.