Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas.
Several types of endocrine tumors show frequent somatic deletions of the distal part of chromosome arm 11q, where the tumor-suppressor gene SDHD (succinate-ubiquinone oxidoreductase subunit D), constitutionally mutated in paragangliomas of the head and neck, is located. In this study, we screened 18 midgut carcinoids, 7 Merkel cell carcinomas, 46 adrenal pheochromocytomas (37 sporadic and 9 familial), and 7 abdominal paragangliomas for loss of heterozygosity (LOH) and/or mutations at the SDHD gene locus. LOH was detected in 5 out of 8 (62%) informative midgut carcinoids, in 9 out of 30 (30%) sporadic pheochromocytomas, in none of the familial pheochromocytomas (0%), and in 1 out of 6 (17%) abdominal paragangliomas. No sequence variants were detected in the pheochromocytomas or paragangliomas. However, two constitutional putative missense mutations, H50R and G12S, were detected in two midgut carcinoids, which were both associated with LOH of the other allele. The same sequence variants were also detected in two Merkel cell carcinomas. In addition, the S68S polymorphism was found to coexist with the G12S sequence variant in both cases. In conclusion, we show that alterations of the SDHD gene seem to be involved in the tumorigenesis of both midgut carcinoids and Merkel cell carcinomas.
Kytölä
Soili
S
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.
Nord
Brita
B
Elder
Elisabeth Edström
EE
Carling
Tobias
T
Kjellman
Magnus
M
Cedermark
Björn
B
Juhlin
Claes
C
Höög
Anders
A
Isola
Jorma
J
Larsson
Catharina
C
D000008:Abdominal Neoplasms / Q000201:enzymology / Q000235:genetics; D000310:Adrenal Gland Neoplasms / Q000201:enzymology / Q000235:genetics; D002276:Carcinoid Tumor / Q000201:enzymology / Q000235:genetics*; D015266:Carcinoma, Merkel Cell / Q000201:enzymology / Q000235:genetics*; D042963:Electron Transport Complex II; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007414:Intestinal Neoplasms / Q000201:enzymology / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics; D009097:Multienzyme Complexes / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*; D010088:Oxidoreductases / Q000235:genetics*; D010235:Paraganglioma / Q000201:enzymology / Q000235:genetics*; D010673:Pheochromocytoma / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics*
D005819:Genetic Markers; D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase