How many pathways to pheochromocytoma?

Pheochromocytomas, like several other tumors, may be either sporadic or the manifestation of a familial cancer syndrome. Recently, major advances have occurred in both the understanding of diverse molecular mechanisms leading to pheochromocytoma and the diagnostic modalities available for detection of the disease. Familial pheochromocytoma may be a manifestation of multiple endocrine neoplasia type 2 (MEN-2), von Hippel-Lindau (VHL), or neurofibromatosis-1 (NF 1) disease. Tumor-suppressor genes responsible for the familial occurrence of extra-adrenal pheochromocytoma, called paraganglioma, have been identified. This wealth of genetic information, coupled with the availability of sensitive and specific biochemical tests as well as imaging studies, allows for genetic screening and early diagnosis of pheochromocytoma. In addition, genetic screening of relatives at risk is now feasible. In this article, we review recent clinical and molecular advances in our understanding of pheochromocytoma.

[1]  H. Neumann,et al.  Pheochromocytomas: detection with 18F DOPA whole body PET--initial results.. , 2002, Radiology.

[2]  Michael I. Wilson,et al.  C. elegans EGL-9 and Mammalian Homologs Define a Family of Dioxygenases that Regulate HIF by Prolyl Hydroxylation , 2001, Cell.

[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]  K. Zerres,et al.  Phaeochromocytoma associated with a de novo VHL mutation as form fruste of von Hippel-Lindau disease , 2001, European Journal of Pediatrics.

[5]  L. Mulligan,et al.  Multiple endocrine neoplasia type 2: molecular aspects. , 2001, Frontiers of hormone research.

[6]  P. Ratcliffe,et al.  Contrasting effects on HIF-1alpha regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease. , 2001, Human molecular genetics.

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

[8]  M. Ivan,et al.  HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O2 Sensing , 2001, Science.

[9]  Michael I. Wilson,et al.  Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation , 2001, Science.

[10]  G. Chatellier,et al.  Factors associated with perioperative morbidity and mortality in patients with pheochromocytoma: analysis of 165 operations at a single center. , 2001, The Journal of clinical endocrinology and metabolism.

[11]  O. Gimm.  Multiple endocrine neoplasia type 2: clinical aspects. , 2001, Frontiers of hormone research.

[12]  T. Dwight,et al.  Sporadic and familial pheochromocytomas are associated with loss of at least two discrete intervals on chromosome 1p. , 2000, Cancer research.

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

[14]  A. Harris,et al.  Identification of novel hypoxia dependent and independent target genes of the von Hippel-Lindau (VHL) tumour suppressor by mRNA differential expression profiling , 2000, Oncogene.

[15]  C. Eng,et al.  Differential genetic alterations in von Hippel-Lindau syndrome-associated and sporadic pheochromocytomas. , 2000, The Journal of clinical endocrinology and metabolism.

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

[17]  M. Ivan,et al.  Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel–Lindau protein , 2000, Nature Cell Biology.

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

[19]  G. Perilongo,et al.  Somatic mosaicism in von Hippel‐Lindau disease , 2000, Human mutation.

[20]  P. Choyke,et al.  Mosaicism in von Hippel-Lindau disease: lessons from kindreds with germline mutations identified in offspring with mosaic parents. , 2000, American journal of human genetics.

[21]  H. Neumann,et al.  Preserved adrenocortical function after laparoscopic bilateral adrenal sparing surgery for hereditary pheochromocytoma. , 1999, The Journal of clinical endocrinology and metabolism.

[22]  M. Gstaiger,et al.  The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activity. , 1999, Genes & development.

[23]  W. Linehan,et al.  Plasma normetanephrine and metanephrine for detecting pheochromocytoma in von Hippel-Lindau disease and multiple endocrine neoplasia type 2. , 1999, The New England journal of medicine.

[24]  C. Wykoff,et al.  The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis , 1999, Nature.

[25]  W. Kaelin,et al.  Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. , 1999, Science.

[26]  R. Klausner,et al.  Transcription-Dependent Nuclear-Cytoplasmic Trafficking Is Required for the Function of the von Hippel-Lindau Tumor Suppressor Protein , 1999, Molecular and Cellular Biology.

[27]  G. Semenza,et al.  Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. , 1999, Annual review of cell and developmental biology.

[28]  R. Deshaies.  SCF and Cullin/Ring H2-based ubiquitin ligases. , 1999, Annual review of cell and developmental biology.

[29]  H. Neumann,et al.  Adrenal‐sparing surgery for phaeochromocytoma , 1999, The British journal of surgery.

[30]  V. Park,et al.  Neurofibromatosis type 1 (NF1): a protein truncation assay yielding identification of mutations in 73% of patients. , 1998, Journal of medical genetics.

[31]  W. Kaelin,et al.  pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[32]  G. Bartsch,et al.  Laparoscopic surgery for pheochromocytoma: adrenalectomy, partial resection, excision of paragangliomas. , 1998, The Journal of urology.

[33]  L. Huang,et al.  Regulation of hypoxia-inducible factor 1α is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway , 1998 .

[34]  H. Neumann,et al.  Genotype–phenotype correlations in von hippel–lindau disease , 1998, Journal of internal medicine.

[35]  Kebin Liu,et al.  Catalytic Domain of the p120 Ras GAP Binds to Rab5 and Stimulates Its GTPase Activity* , 1998, The Journal of Biological Chemistry.

[36]  W. Linehan,et al.  Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas. , 1998, Cancer research.

[37]  W. Kaelin,et al.  Regulation of Hypoxia-Inducible mRNAs by the von Hippel-Lindau Tumor Suppressor Protein Requires Binding to Complexes Containing Elongins B/C and Cul2 , 1998, Molecular and Cellular Biology.

[38]  W. Linehan,et al.  Improved detection of germline mutations in the von Hippel‐Lindau disease tumor suppressor gene , 1998, Human mutation.

[39]  A. Vortmeyer,et al.  Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas. , 1997, The American journal of pathology.

[40]  H. Neumann,et al.  Functioning thoracic paraganglioma: association with Von Hippel-Lindau syndrome. , 1997, The Journal of clinical endocrinology and metabolism.

[41]  B. Korf,et al.  The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. , 1997, JAMA.

[42]  M. Cayouette,et al.  Homozygous inactivation of the NF1 gene in bone marrow cells from children with neurofibromatosis type 1 and malignant myeloid disorders. , 1997, The New England journal of medicine.

[43]  M. Emmert-Buck,et al.  von Hippel-Lindau gene deletion detected in the stromal cell component of a cerebellar hemangioblastoma associated with von Hippel-Lindau disease. , 1997, Human pathology.

[44]  B. Zbar,et al.  Renal cysts, renal cancer and von Hippel-Lindau disease. , 1997, Kidney international.

[45]  W. Linehan,et al.  Allelic deletions of the VHL gene detected in multiple microscopic clear cell renal lesions in von Hippel-Lindau disease patients. , 1996, The American journal of pathology.

[46]  R. Klausner,et al.  Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[47]  W. Kaelin,et al.  Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[48]  C. Eng.  Seminars in medicine of the Beth Israel Hospital, Boston. The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung's disease. , 1996, New England Journal of Medicine.

[49]  D. Viskochil,et al.  Identification of NF1 mutations in both alleles of a dermal neurofibroma , 1996, Nature Genetics.

[50]  F. Chen,et al.  Genotype-phenotype correlation in von Hippel-Lindau disease: identification of a mutation associated with VHL type 2A. , 1996, Journal of medical genetics.

[51]  J. D. van der Walt,et al.  Carotid body paraganglioma in von Hippel‐Lindau disease: a rare association , 1996, Histopathology.

[52]  H. Höfler,et al.  Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe , 1996, Human Genetics.

[53]  M. Borrello,et al.  The full oncogenic activity of Ret/ptc2 depends on tyrosine 539, a docking site for phospholipase Cgamma , 1996, Molecular and cellular biology.

[54]  A. Webster,et al.  Phenotypic expression in von Hippel-Lindau disease: correlations with germline VHL gene mutations. , 1996, Journal of medical genetics.

[55]  W. Linehan,et al.  Germline mutations in the Von Hippel‐Lindau disease (VHL) gene in families from North America, Europe, and Japan , 1996, Human mutation.

[56]  B. Ponder,et al.  Consequences of direct genetic testing for germline mutations in the clinical management of families with multiple endocrine neoplasia, type II. , 1995, JAMA.

[57]  A. Pandey,et al.  The Ret Receptor Protein Tyrosine Kinase Associates with the SH2-containing Adapter Protein Grb10 (*) , 1995, The Journal of Biological Chemistry.

[58]  D. Duan,et al.  Inhibition of transcription elongation by the VHL tumor suppressor protein , 1995, Science.

[59]  A. Kibel,et al.  Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C , 1995, Science.

[60]  S. Colman,et al.  Benign neurofibromas in type 1 neurofibromatosis (NF1) show somatic deletions of the NF1 gene , 1995, Nature Genetics.

[61]  R. Heim,et al.  Distribution of 13 truncating mutations in the neurofibromatosis 1 gene. , 1995, Human molecular genetics.

[62]  K. Plate,et al.  Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastomas. , 1995, Cancer research.

[63]  L. Liotta,et al.  A microdissection technique for archival DNA analysis of specific cell populations in lesions < 1 mm in size. , 1995, The American journal of pathology.

[64]  S. Richard,et al.  Pheochromocytoma as the first manifestation of von Hippel-Lindau disease. , 1994, Surgery.

[65]  J. Herman,et al.  Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Constancio González,et al.  Carotid body chemoreceptors: from natural stimuli to sensory discharges. , 1994, Physiological reviews.

[67]  T. Shuin,et al.  Somatic mutations of the von Hippel-Lindau tumor suppressor gene in sporadic central nervous system hemangioblastomas. , 1994, Cancer research.

[68]  M. Lerman,et al.  Identification of intragenic mutations in the von Hippel-Lindau disease tumour suppressor gene and correlation with disease phenotype. , 1994, Human molecular genetics.

[69]  T. Sugimura,et al.  Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis. , 1994, Cancer research.

[70]  T. Sugiyama,et al.  Frequent overexpression of vascular endothelial growth factor gene in human renal cell carcinoma. , 1994, The Tohoku journal of experimental medicine.

[71]  A Greco,et al.  The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins. , 1994, Oncogene.

[72]  Y Kubota,et al.  Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas. , 1994, Cancer research.

[73]  J. Brooks,et al.  Mutations of the VHL tumour suppressor gene in renal carcinoma , 1994, Nature Genetics.

[74]  Frank Costantini,et al.  Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret , 1994, Nature.

[75]  P. Devilee,et al.  Further Localization of the Gene for Hereditary Paragangliomas and Evidence for Linkage in Unrelated Families , 1994, European journal of human genetics : EJHG.

[76]  F. Costantini,et al.  Expression of the c-ret proto-oncogene during mouse embryogenesis. , 1993, Development.

[77]  H. Neumann,et al.  Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease. , 1993, The New England journal of medicine.

[78]  B. Ponder,et al.  Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A , 1993, Nature.

[79]  J. Gnarra,et al.  Identification of the von Hippel-Lindau disease tumor suppressor gene. , 1993, Science.

[80]  M. Gagner,et al.  Laparoscopic adrenalectomy in Cushing's syndrome and pheochromocytoma. , 1992, The New England journal of medicine.

[81]  Barry F. Smith,et al.  Loss of NF1 alleles in phaeochromocytomas from patients with type 1 neurofibromatosis , 1992, Genes, chromosomes & cancer.

[82]  M. Wigler,et al.  The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins , 1990, Cell.

[83]  F. Tamanoi,et al.  The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae , 1990, Cell.

[84]  P. O’Connell,et al.  The GAP-related domain of the neurofibromatosis type 1 gene product interacts with ras p21 , 1990, Cell.

[85]  Jeng-Shin Lee,et al.  Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[86]  P. Rowley,et al.  Molecular genetic analysis of tumors in von recklinghausen neurofibromatosis: Loss of heterozygosity for chromosome 17 , 1989, Genes, chromosomes & cancer.

[87]  T. Iwamoto,et al.  Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. , 1988, Oncogene.

[88]  E. Gelmann,et al.  Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. , 1988, Annals of internal medicine.

[89]  K. Kidd,et al.  Assignment of multiple endocrine neoplasia type 2A to chromosome 10 by linkage , 1987, Nature.

[90]  Y. Nakamura,et al.  Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. , 1987, Science.

[91]  C. Mathew,et al.  A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10 , 1987, Nature.

[92]  Robert W. Miller,et al.  Neurofibromatosis and childhood leukemia. , 1978 .