New insights into the genetics of familial chromaffin cell tumors

Annals of the New York Academy of Sciences

Volumn 970, Issue , 2002, Pages 11-28

  Koch, Christian A ^a,c   Vortmeyer, Alexander O ^b   Zhuang, Zhengping ^b   Brouwers, Frederieke M ^a   Pacak, Karel ^a  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

^b NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

^c NONE   (Germany)

Author keywords

Multiple endocrine neoplasia type 2; NF1; Paraganglioma; Pheochromocytoma; RET; SDHB; SDHC; SDHD; Second hit; Tumor formation; VHL

Indexed keywords

CATECHOLAMINE; MITOCHONDRIAL COMPLEX II; MITOCHONDRIAL ENZYME; MUTANT PROTEIN; PROTEIN RET; UNCLASSIFIED DRUG;

ADRENAL MEDULLA; ALLELE; CATECHOLAMINE RELEASE; CHROMAFFIN CELL; CONFERENCE PAPER; FAMILIAL DISEASE; GENE DELETION; GENE MUTATION; GENETICS; GERM LINE; HUMAN; MULTIPLE ENDOCRINE NEOPLASIA; NEUROFIBROMATOSIS; PARAGANGLIOMA; PHEOCHROMOCYTOMA; RESPIRATORY CHAIN; TUMOR GROWTH; VON HIPPEL LINDAU DISEASE;

EID: 0037024507     PISSN: 00778923     EISSN: None     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2002.tb04409.x     Document Type: Conference Paper

References (112)

1. Lack, E.E. 1994. Pathology of Adrenal and Extraadrenal Paraganglia. W.B. Saunders. Philadelphia, PA.
2. Lack, E.E. 1997. Tumors of the Adrenal and Extraadrenal Paraganglia. Armed Forces Institute of Pathology. Washington, DC.
3. Whalen, R.K., A.F. Althausen & G.H. Daniels. 1992. Extraadrenal pheochromocytoma. J. Urol. 147: 1-10.
4. Lack, E.E., A.R. Perez-Atayde & J.B. Young. 1986. Carotid bodies in sudden infant death syndrome: A combined light microscopic, ultrastructural and biochemical study. Ped. Pathol. 6: 335-350.
5. Zapata, P., A. Hess, E.L. Bliss, et al. 1969. Chemical, electron microscopic and physiological observations on the role of catecholamines in the carotid body. Brain Res. 14: 473-496.
6. Gimm, O., M. Armanios, H. Dziema, et al. 2000. Somatic and occult germline mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma. Cancer Res. 60: 6822-6825.
7. Bender, B.U., M. Gutsche, S. Glasker, et al. 2000. Differential genetic alterations in von Hippel-Lindau syndrome-associated and sporadic pheochromocytomas. J. Clin. Endocrinol, Metab. 85: 4568-4574.
8. Hansford, J.R. & L.M. Mulligan. 2000. Multiple endocrine neoplasia type 2 (MEN 2) and RET: from neoplasia to neurogenesis. J. Med. Genet. 37: 817-827.
9. Jhiang, S.M. 2000. The RET protooncogene in human cancers. Oncogene 19: 5590-5597.
10. Baysal, B.E., R.E Ferrell, J.E. Willett-Brozick, et al. 2000. Mutations in SDHD, a mitochondrial complex II gene in hereditary paraganglioma. Science 287: 848-851.
11. Niemann, S. & U. Muller. 2000. Mutations in SDHC cause autosomal dominant paraganglioma type 3. Nat. Genet. 26: 268-270.
12. Walther, M.M., R. Reiter, H.R. Keiser, et al. 1999. Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: Comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma. J. Urol. 162: 659-664.
13. Korf, B.R. 2000. Malignancy in neurofibromatosis type 1. The Oncologist 5: 477-485.
14. Walther, M.M., J. Herring, E. Enquist, et al. 1999. Von Recklinghausen's disease and pheochromocytomas. J. Urol. 162: 1582-1586.
15. Pacak, K., G.P. Chrousos, C.A. Koch, et al. 2001. Pheochromocytoma: progress in diagnosis, therapy, and genetics. In Adrenal Disorders. A. Margioris & G.P. Chrousos, Eds.:379-413. Humana Press. New York.
16. Eng, C. 1999. RET protooncogene in the development of human cancer. J. Clin. Oncol. 17: 380-393.
17. Nilsson, O., L.E. Tisell, S. Jansson, et al. 1999. Adrenal and extraadrenal pheochromocytomas in a family with germline RET V804L mutation. JAMA 281: 1587-1588.
18. Astuti, D., F. Latif, A. Dallol, et al. 2001. Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am. J. Hum. Genet. 69: 49-54.
19. Baysal, B., W.S. Rubinstein & P.E.M. Taschner 2001. Phenotypic dichotomy in mitochondrial complex II genetic disorders. J. Mol. Med. 79: 495-503.
20. Koch, C.A., D. Mauro, M.M. Walther, et al. 2002. Pheochromocytomas in VHL disease: Distinct histopathologic phenotype compared to pheochromocytoma in multiple endocrine neoplasia type 2. Endocr. Pathol. 13: 17-27.
21. Eng C., P.A. Crossey, L.M. Mulligan, et al. 1995. Mutations in the RET proto-oncogene and the von Hippel-Lindau disease tumor suppressor gene in sporadic and syndromic pheochromocytomas. J. Med. Genet. 32: 934-937.
22. Van Der Harst, E., R.R. De Kruger, W.N. Dinjens, et al. 1998. Germline mutations in the VHL gene in patients presenting with pheochromocytoma. Int. J. Cancer 77: 337-340.
23. Wohlk, N., G.J. Cote, M.M. Bugalho, et al. 1996. Relevance of RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. J. Clin. Endocrinol. Metab. 81: 3740-3745.
24. Decker, R.A., M.L. Peacock, M.J. Borst, et al. 1995. Progress in genetic screening of multiple endocrine neoplasia type 2A: Is calcitonin obsolete? Surgery 118: 257-263.
25. Sipple, J.H. 1961. The association of pheochromocytoma with carcinoma of the thyroid gland. Am. J. Med. 31: 163-166.
26. Gagel, R.F. 2001. Multiple endocrine neoplasia type 2. In DeGroot's Endocrinology, 4th Ed. L. DeGroot & J.L. Jameson, Eds.: Vol. 3: 2518-2532. W.B. Saunders. Philadelphia, PA.
27. Eng, C. 1996. Seminars in medicine of the Beth Israel Hospital, Boston. The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung's disease. N. Engl. J. Med. 335: 943-951.
28. Borst, M.J., J.M. Vancamp, M.L. Peacock, et al. 1995. Mutational analysis of multiple endocrine neoplasia type 2A associated with Hirschsprung's disease. Surgery 117: 386-391.
29. Decker, R.A., & M.L. Peacock, 1998. Occurrence of MEN2a in familial Hirschsprung's disease: A new indication for genetic testing of the RET protooncogene. J. Pediatr. Surg. 33: 207-214.
30. Carney, J.A., V.L. Go, G.W. Sizemore, et al. 1976. Alimentary-tract ganglioneuromatosis: A major component of the syndrome of multiple endocrine neoplasia type 2b. N. Engl. J. Med. 295: 1287-1291.
31. Mulligan, L.M., C. Eng, C.S. Healey, et al. 1994. Specific mutations of the RET proto-oncogene are related to disease phenotype in MEN 2A and FMTC. Nat. Genet. 6: 70-74.
32. Takahashi, M., J. Ritz & G.M. Cooper. 1985. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell 42: 581-588.
33. Takahashi, M. 2001. The GDNF/RET signaling pathway and human diseases. Cytokine Growth Factor Rev. 12: 361-373.
34. Jing, S., D. Wen, Y. Yu, et al. 1996. GDNF-induced activation of the RET protein tyrosine kinase is mediated by GDNFR-α, a novel receptor for GDNF. Cell 85: 1113-1124.
35. Trupp, M., E. Arenas, M. Fainzilber, et al. 1996. Functional receptor for GDNF encoded by the c-ret proto-oncogene. Nature 381: 785-789.
36. Santoro, M., F. Carlomagno, A. Romano, et al. 1995. Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 267: 381-383.
37. Schuchardt, A., V. D'Agati, L. Larsson-Blomberg, et al. 1994. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor ret. Nature 367: 380-382.
38. Manie, S., M. Santoro, A. Fusco, et al. 2001. The RET receptor: Function in development and dysfunction in congenital malformation. Trends Genet. 17: 580-589.
39. Delellis, R., H.J. Wolfe, R.F. Gagel, et al. 1976. Adrenal medullary hyperplasia. Am. J. Pathol. 83: 177-196.
40. Carney, J.A., G.W. Sizemore & G.M. Tyce. 1975. Bilateral adrenal medullary hyperplasia in multiple endocrine neoplasia type 2: The precursor of bilateral pheochromocytoma. Mayo Clin. Proc. 50: 3-10.
41. Zhuang, Z., W.S. Park, S. Pack, et al. 1998. Trisomy 7-harboring non-random duplication of the mutant MET allele in hereditary papillary renal carcinomas. Nat. Genet. 20: 66-69.
42. Huang, S.C., C.A. Koch, A.O. Vortmeyer, et al. 2000. Duplication of the mutant RET allele in trisomy 10 or loss of the wild-type allele in multiple endocrine neoplasia type 2-associated pheochromocytoma. Cancer Res. 60: 6223-6226.
43. Koch, C.A., S.C. Huang, J.F. Moley, et al. 2001. Allelic imbalance between the mutant and wild-type RET allele in MEN 2A-associated medullary thyroid carcinoma. Oncogene 20: 7809-7811.
44. Cooley, L.D., F.F.B. Elder, A. Knuth, et al. 1995. Cytogenetic characterization of three human and three rat medullary thyroid carcinoma cell lines. Cancer Genet. Cytogenet. 80: 138-149.
45. Huang, S.C. et al. Unpublished data.
46. Zhang, Z., Y. Wang, H.G. Vikis, et al. 2001. Wildtype kras2 can inhibit lung carcinogenesis in mice. Nat. Genet. 29: 25-33.
47. Pfeifer, G. 2001. A new verdict for an old convict. Nat. Genet 29: 3-4.
48. Koch, C.A., S.C. Huang, A.O. Vortmeyer, et al. 2000. A patient with MEN 2 and multiple mutations of RET in the germline. Exp. Clin. Endocrinol. Diabetes 108: 493.
49. Bartsch, D.C., C. Hasse, C. Schug, et al. 2000. A RET double mutation in the germline of a kindred with FMTC. Exp. Clin. Endocrinol. Diabetes 108: 128-132.
50. Tessitore, A., A.A. Sinisi, D. Pasquali, et al. 1999. A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene. J. Clin. Endocrinol. Metab. 84: 3522-3527.
51. Menko, F.H., R.B. Van Der Luijt, I.A.J. De Valk, et al. 2002. A typical MEN 2B associated with two germline RET mutations on the same allele not involving codon 918. J. Clin. Endocrinol. Metab. 87: 393-397.
52. Mulligan, L.M., E. Gardner, B.A. Smith, et al. 1993. Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2. Genes Chromosomes Cancer 6: 166-177.
53. Moley, J.F., M.B. Brother, C.T. Fong, et al. 1992. Consistent association of 1p loss of heterozygosity with pheochromocytomas from patients with multiple endocrine neoplasia type 2 syndromes. Cancer Res. 52: 770.
54. Benn, D.E., T. Dwight, A.L. Richardson, et al. 2000. Sporadic and familial pheochromocytomas are associated with loss of at least two discrete intervals on chromosome 1p. Cancer Res. 60: 7048-7051.
55. Dannenberg, H., E.J. Speel, J. Zhao, et al. 2000. Losses of chromosomes 1p and 3q are early genetic events in the development of sporadic pheochromocytomas. Am. J. Pathol. 157: 353-359.
56. Khosla, S., V.M. Patel, I.D. Hay, et al. 1991. Loss of heterozygosity suggests multiple genetic alterations in pheochromocytomas and medullary thyroid carcinomas. J. Clin. Invest. 87: 1691-1699.
57. Zhuang, Z., P. Bertheau, M.R. Emmert-Buck, et al. 1995. A microdissection technique for archival DNA analysis of specific cell populations in less than 1 mm in size. Am. J. Pathol. 146: 620-625.
58. Zhuang, Z. & A.O. Vortmeyer. 1998. Applications of tissue microdissection in cancer genetics. Cell Vis. 5: 43-48
59. Thibodeau, S.N., N.M. Lindor, R. Honchel, et al. 1994. Mutations in the RET proto-oncogene in sporadic pheochromocytomas. Am. J. Hum. Genet. 55: A71.
60. Hofstra, R.M.W., T. Stelwagen, R.P. Stulp, et al. 1996. Extensive mutation scanning of RET in sporadic medullary thyroid carcinoma and of RET and VHL in sporadic pheochromocytoma reveals involvement of these genes in only a minority of cases. J. Clin. Endocrinol. Metab. 81: 2881-2884.
61. Bar, M., E. Friedman, O. Jakobovitz, et al. 1997. Sporadic pheochromocytomas are rarely associated with germline mutations in the von Hippel-Lindau and RET genes. Clin. Endocrinol. 47: 707-712.
62. Brauch, H., W, Hoppner, H. Jahnig, et al. 1997. Sporadic pheochromocytoman are rarely associated with germline mutations in the VHL tumor suppressor gene or the RET protooncogene. J. Clin. Endocrinol. Metab. 82: 4101-4104.
63. Lindor, N.M., R. Honchel, S. Khosla, et al. 1995. Mutations in the RET proto-oncogene in sporadic pheochromocytomas. J. Clin. Endocrinol. Metab. 80: 627-629.
64. Beldjord, C., F. Desclaux-Arramond, M. Raffin-Sanson, et al. 1995. The RET protooncogene in sporadic pheochromocytomas: frequent MEN 2-like mutations and new molecular defects. J. Clin. Endocrinol. Metab. 80: 2063-2067.
65. Januszewicz, A., H.P. Neumann, J. Lon, et al. 2000. Incidence and clinical relevance of RET protooncogene germline mutations in pheochromocytoma patients. J. Hypertens. 18: 1019-1023.
66. Komminoth, P., J. Roth, S. Muletta, et al. 1996. RET proto-oncogene point mutations in sporadic neuroendocrine tumors. J. Clin. Endocrinol. Metab. 81: 2-41-6
67. Chew, S.L., P. Lavender, A. Jain, et al. 1995. Absence of mutations in the MEN 2A region of the ret protooncogene in non MEN 2A pheochromocytomas. Clin. Endocrinol. 42: 17-21.
68. Crossey, P.A., C. Eng, M. Ginalska-Malinowska, et al. 1995. Molecular genetic diagnosis of von Hippel-Lindau disease. J. Med. Genet. 312: 885-886.
69. Koch, C.A., S.C. Huang, Z. Zhuang, et al. 2002. Somatic VHL gene deletion and point mutation in MEN 2A-associated pheochromocytoma. Oncogene 21: 479-482
70. Kondo, K. & W.G. Kaelin. 2001. The von Hippel-Lindau tumor suppressor gene. Exp. Cell Res. 264: 117-125.
71. Neumann, H.P. & O.D. Wiestler. 1991, Clustering of features of von Hippel-Lindau syndrome: Evidence for a complex genetic locus. Lancet 337: 10521054.
72. Maher, E.R., J.R. Yates, R. Harries, et al. 1990. Clinical features and natural history of von Hippel-Lindau disease. Quart. J. Med. 77:1151-1163.
73. Richard, S., D. Chaveau, Y. Chretien, et al. 1994. Renal lesions and pheochromocytoma in von Hippel-Lindau disease. Adv. Nephrol. 23: 1-27.
74. Neumann, H.P., D.P. Berger, G. Sigmund, et al. 1993. Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease. N. Engl. J. Med. 329: 1531-1538.
75. Crossey, P.A., F.M. Richards, K. Foster, et al. 1994. Identification of intragenic mutations in the von Hippel-Lindau disease tumor suppressor gene and correlations with disease phenotype. Human Mol. Genet. 3: 1303-1308.
76. Ritter, M,M., A. Frilling, P.A. Crossey, et al. 1996. Isolated familial pheochromocytoma as a variant of von Hippel-Lindau disease. J. Clin. Endocrinol. Metab. 81: 1035-1037.
77. Zbar, B., T. Kishida, F. Chen, et al. 1996. Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan. Hum. Mutat. 8: 348-357.
78. Brauch, H., T. Kishida, D. Glavac, et al. 1995. Von Hippel-Lindau disease with pheochromocytoma in the Black Forest region of Germany: Evidence for a founder effect. Hum. Genet. 95: 551-556.
79. Gross, D.J., N. Avishai, V. Meiner, et al. 1996. Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene. J. Clin. Endocrinol. Metab. 81: 147-149.
80. Duan, D.R., A. Pause, W.H. Burgess, et al. 1995. Inhibition of transcription elongation by the VHL tumor suppressor protein. Science 269:1402-1407.
81. Aso, T., W.S. Lane, J.W. Conaway, et al. 1995. Elongin: A multisubunit regulator of elongation by RNA polymerase II. Science 269: 1439-1443.
82. Vortmeyer, A.O., S.C. Huang, S.D. Pack, et al. 2002. Somatic point mutation of the wildtype allele detected in tumors of patients with VHL germline deletion. Oncogene 21:1167-1170.
83. Neumann, H.P.H., S. Glasker, B:U. Bender, et al. 2001. Molecular Classification of 270 Patients with Symptomatic Pheochromocytoma. [abstract].
84. Chen, F., T. Kishida & M. Yao. 1995. Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: Correlations with phenotype. Hum. Mutat. 5: 66-75
85. Zeiger, M.A., B. Zbar, H. Keiser, et al. 1995. Loss of heterozygosity on the short arm of chromosome 3 in sporadic, von Hippel-Lindau disease-associated, and familial pheochromocytoma. Genes Chromosomes Cancer 13:151-156.
86. Lubensky, I.A., J.R. Gnarra, P. Bertheau, et al. 1996. Allelic deletion of the VHL gene detected in multiple microscopic clear cell renal lesions in von Hippel-Lindau disease patients. Am. J. Pathol. 149:2089-2094
87. Gutmann, D.H. & F.S. Collins. 1998. Neurofibromatosis type 1. In The Genetic Basis of Human Cancer B. Vogelstein & K.W. Kinzler, Eds.:443-442. McGraw-Hill. New York.
88. Riccardi, V.M. 1991. Von Recklinghausen neurofibromatosis. N. Engl. J. Med. 305: 1617-1627.
89. Stacey, D. & A. Kazlauskas. 2002 Regulation of RAS signaling by the cell cycle Curr. Opin. Genet. Dev. 12: 44-46.
90. Jacks, T., T.S. Shih, E.M. Schmitt, et al. 1994. Tumour predisposition in mice heterozygous for a targeted mutation in NF1. Nat. Genet. 7: 353-361
91. Xu, W., L.M. Mulligan, M.A. Ponder, et al. 1992. Loss of NF1 alleles in pheochromocytomas from patients with typel neurofibromatosis. Genes Chrom. Cancer 4: 337-342.
92. Gutmann D.H., J.L. Cole, W.J. Stone, et al. 1994. Loss of neurofibromin in adrenal gland tumors from patients with neurofibromatosis type 1. Genes Chromosomes Cancer 10: 55-58.
93. Gutmann, D.H., R.T. Geist, K. Rose, et al. 1995 Loss ofneurofibromatosis type 1 gene expression in pheochromocytomas from patients without NF1, Genes Chromosomes Cancer 13: 104-109,
94. Oosterwijk, J.C., J.C. Jansen, E.M, Van Schothorst, et al, 1996, First experiences with genetic counselling based on predictive DNA diagnosis in hererditary glomus tumors (paragangliomas). J. Med. Genet. 33: 379-383.
95. Erickson, D., Y.C. Kudva, M.J. Ebersold, et al. 2001. Benign paragangliomas: Clinical presentation and treatment outcomes in 236 patients. J. Clin. Endocrinol. Metab. 86: 5210-5216.
96. KOCH, C.A., K. PACAK & G.P. CHROUSOS, 2002, Endocrine tumors, In Principles and Practice of Pediatric Oncology, 4th Ed, P.A, Pizzo & D,G, Poplack, Eds.:1115-1146. Lippincott Williams & Wilkins, Philadelphia, PA.
97. Koch, C.A., N. Azumi, M,A. Furlong, et al, 1999, Carcinoid syndrome caused by an atypical carcinoid of the uterine cervix. J. Clin. Endocrinol. Metab. 84: 4209-4213.
98. Arias-Stella, J, & J. Valcarcel. 1973, The human carotid body at high altitudes. Pathol. Microbiol. 39: 292-297.
99. Pacheco-Ojeda, L., E. Durango, C, Rodriquez, et al. 1988. Carotid body tumors at high altitudes: Quito, Ecuador, 1987, World J. Surg. 12: 856-860.
100. Edwards, C., D. Heath & P. Harris. 1971. The carotid body in emphysema and left ventricular hypertrophy. J. Pathol. 104: 1-13.
101. Lack, E.E. 1978. Hyperplasia of vagal and carotid body paraganglia in patients with chronic hypoxemia. Am. J. Pathol, 91: 497-516.
102. Lack, E.E. 1977. Carotid body hypertrophy in patients with cystic fibrosis and cyanotic congenital heart disease. Hum. Pathol. 8:39-51.
103. Boersma, H.H., J.W. Wensing, T.L. Kho, et al. 2002 Compensatory uptake of I-123 MIBG in the contralateral adrenal gland after removal of a pheochromocytoma. Clin. Nucl. Med. 27: 113-116.
104. Baysal, B.E., J.E. Willet-Brozick, P.E. Taschner, et al. 2001. A high-resolution integrated map spanning the SDHD gene at 11q23: A 1.1-Mb BAC contig, a partial transcript map and fifteen new repeat polymorphisms in a tumor suppressor region. Eur. J. Hum. Genet. 9: 121-129.
105. Mariman, E.G., S.E. Van Beersum, C.W. Cremers, et al. 1995. Fine mapping of a putatively imprinted gene for familial nonchromaffin paragangliomas to chromosome llq13.1: Evidence for genetic heterogeneity. Hum. Genet. 95: 56-62.
106. Devilee, P., E.M. Van Schothorst, A.F. Bardoel, et al. 1994. Allelotype of head and neck paragangliomas: Allelic imbalance is confined to the long arm of chromosome 11, the site of the predisposing locus PGL. Genes Chromosomes Cancer 11: 71-78.
107. Van Schothorst, E.M., M. Beekman, P. Torremans, et al. 1998. Paragangliomas of the head and neck region show complete loss of heterozygosity at 11q22-23 in chief cells and the flow-sorted DNA aneuploid fraction. Hum. Pathol. 29: 1045-1049.
108. Vargas, M.P., Z. Zhuang, C. Wang, et al. 1997. Loss of heterozygosity on the short arm of chromosomes 1 and 3 in sporadic pheochromocytoma and extraadrenal paraganglioma. Hum. Pathol. 28: 411-415.
109. Tsutsumi, M., Y. Yokota, T. Kakizoe, et al. 1989. Loss of heterozygosity on chromosome 1p and 11p in sporadic pheochromocytoma. J. Natl. Cancer Inst. 81: 367-370.
110. Mathew, C.G.P., K.S. Chin, D.F. Easton, et al. 1987. A linked genetic marker for multiple endocrine neoplasia type 2A on chromosome 10. Nature 328: 528-530.
111. Rodien, P., X. Jeunemaitre, C. Dumont, et al. 1997. Genetic alterations of the RET proto-oncogene in familial and sporadic pheochromocytomas. Horm. Res. 47: 263-268.
112. Neumann, H.P. et al. 2002. Germline mutations in nonsyndromic pheochromocytoma. N. Engl. J. Med. 346: 1486-1488.