A novel candidate region linked to development of both pheochromocytoma and head/neck paraganglioma.
Although the histologic distinction between pheochromocytomas and head and neck paragangliomas is clear, little is known about the genetic differences between them. To date, various sets of genes have been found to be involved in inherited susceptibility to developing both tumor types, but the genes involved in sporadic pathogenesis are still unknown. To define new candidate regions, we performed CGH analysis on 29 pheochromocytomas and on 24 paragangliomas mainly of head and neck origin (20 of 24), which allowed us to differentiate between the two tumor types. Loss of 3q was significantly more frequent in pheochromocytomas, and loss of 1q appeared only in paragangliomas. We also found gain of 11q13 to be a significantly frequent alteration in malignant cases of both types. In addition, recurrent loss of 8p22-23 was found in 62% of pheochromocytomas (including all malignant cases) versus in 33% of paragangliomas, suggesting that this region contains candidate genes involved in the pathogenesis of this abnormality. Using FISH analysis on tissue microarrays, we confirmed genomic deletion of this region in 55% of pheochromocytomas compared to 12% of paragangliomas. Loss of 8p22-23 appears to be an important event in the sporadic development of these tumors, and additional molecular studies are necessary to identify candidate genes in this chromosomal region.
Cascón
Alberto
A
Hereditary Endocrine Cancer Group, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.
Ruiz-Llorente
Sergio
S
Rodríguez-Perales
Sandra
S
Honrado
Emiliano
E
Martínez-Ramírez
Angel
A
Letón
Rocío
R
Montero-Conde
Cristina
C
Benítez
Javier
J
Dopazo
Joaquín
J
Cigudosa
Juan C
JC
Robledo
Mercedes
M
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D010235:Paraganglioma / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*
D014408:Biomarkers, Tumor