Chromosomal changes in sporadic and familial head and neck paragangliomas.
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.


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.
Sevilla
María A
MA
Department of Otolaryngology, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
Hermsen
Mario A
MA
Weiss
Marjan M
MM
Grimbergen
Anneliese
A
Balbín
Milagros
M
Llorente
José Luis
JL
Rodrigo
Juan Pablo
JP
Suárez
Carlos
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C497446:VHL protein, human