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. © 2002 Wiley‐Liss, Inc.

[1]  C. Larsson,et al.  Loss of Heterozygosity on the Short Arm of Chromosome 1 in Pheochromocytoma and Abdominal Paraganglioma , 2002, World Journal of Surgery.

[2]  P. Devilee,et al.  Nearly all hereditary paragangliomas in The Netherlands are caused by two founder mutations in the SDHD gene , 2001, Genes, chromosomes & cancer.

[3]  E S Husebye,et al.  Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. , 2001, American journal of human genetics.

[4]  P. Schofield,et al.  Novel mutations in the SDHD gene in pedigrees with familial carotid body paraganglioma and sensorineural hearing loss , 2001, Genes, chromosomes & cancer.

[5]  R. Aguiar,et al.  Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas. , 2001, The Journal of clinical endocrinology and metabolism.

[6]  J. Milunsky,et al.  Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma. , 2001, American journal of medical genetics.

[7]  C. Larsson,et al.  Comparative genomic hybridization identifies loss of 18q22-qter as an early and specific event in tumorigenesis of midgut carcinoids. , 2001, The American journal of pathology.

[8]  D. Evans,et al.  Germline SDHD mutation in familial phaeochromocytoma , 2001, The Lancet.

[9]  C. Eng,et al.  Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma. , 2000, Cancer research.

[10]  Ulrich Müller,et al.  Mutations in SDHC cause autosomal dominant paraganglioma, type 3 , 2000, Nature Genetics.

[11]  R. Ravazzolo,et al.  A single-nucleotide polymorphic variant of the RET proto-oncogene is underrepresented in sporadic Hirschsprung disease , 2000, European Journal of Human Genetics.

[12]  B. Devlin,et al.  Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. , 2000, Science.

[13]  C. Larsson,et al.  Comparative genomic hybridization reveals frequent losses of chromosomes 1p and 3q in pheochromocytomas and abdominal paragangliomas, suggesting a common genetic etiology. , 2000, The American journal of pathology.

[14]  C. Larsson,et al.  Sporadic follicular thyroid tumors show loss of a 200‐kb region in 11q13 without evidence for mutations in the MEN1 gene , 1999, Genes, chromosomes & cancer.

[15]  M. Taniwaki,et al.  Characterization of the human SDHD gene encoding the small subunit of cytochrome b (cybS) in mitochondrial succinate-ubiquinone oxidoreductase. , 1999, Biochimica et biophysica acta.

[16]  D. Neuberg,et al.  Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation , 1999, Oncogene.

[17]  C. Larsson,et al.  Genotyping of adrenocortical tumors: very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16. , 1999, The Journal of clinical endocrinology and metabolism.

[18]  E. Speel,et al.  MEN1 Gene mutation analysis of sporadic adrenocortical lesions , 1999, International journal of cancer.

[19]  B. Allolio,et al.  MEN 1 Gene Analysis in Sporadic Adrenocortical Neoplasms * , 1998 .

[20]  F. Speleman,et al.  Characteristic pattern of chromosomal gains and losses in Merkel cell carcinoma detected by comparative genomic hybridization. , 1998, Cancer research.

[21]  M. Taniwaki,et al.  Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23. , 1997, Cytogenetics and cell genetics.

[22]  M. Stratton,et al.  Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus , 1996, Nature Genetics.

[23]  S. Devries,et al.  Analysis of changes in DNA sequence copy number by comparative genomic hybridization in archival paraffin-embedded tumor samples. , 1994, The American journal of pathology.