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Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas
Author(s) -
Kytölä Soili,
Nord Brita,
Edström Elder Elisabeth,
Carling Tobias,
Kjellman Magnus,
Cedermark Björn,
Juhlin Claes,
Höög Anders,
Isola Jorma,
Larsson Catharina
Publication year - 2002
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.10081
Subject(s) - sdhd , biology , loss of heterozygosity , merkel cell , midgut , multiple endocrine neoplasia type 2 , locus (genetics) , pheochromocytoma , merkel cell carcinoma , cancer research , pathology , genetics , germline mutation , gene , allele , carcinoma , medicine , endocrinology , mutation , botany , larva
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. © 2002 Wiley‐Liss, Inc.