Mutation analysis of glial cell line-derived neurotrophic factor (GDNF), a ligand for the RET/GDNF receptor α complex, in sporadic phaeochromocytomas

Patricia L Dahia, Sergio P A Toledo, Lois M. Mulligan, Eamonn R. Maher, Ashley B. Grossman, Charis Eng

Research output: Contribution to journalArticle

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Abstract

Phaeochromocytomas usually occur sporadically but may also be a feature of three autosomal dominantly inherited cancer syndromes, multiple endocrine neoplasia type 2, von Hippel-Lindau disease (VHL), and, very rarely, type I neurofibromatosis. Germ-line missense mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, cause multiple endocrine neoplasia type 2. In VHL, germ-line mutations in one of the three exons of the VHL tumor suppressor gene have been found in the majority of families. Whereas somatic mutations in the VHL gene have been common in sporadic renal cell carcinoma, a component cancer of VHL, somatic mutations in the RET and VHL genes together have been found in approximately 10T of sporadic phaeochromocytomas. Hence, other genes must also contribute to the pathogenesis of sporadic phaeochromocytomas. Recent data have suggested that glial cell line-derived neurotrophic factor (GDNF) is a ligand for RET and acts via a heterotetrameric receptor complex that includes GDNF receptor α, which provides ligand binding capabilities, and RET, which provides the signaling component. Thus, both GDNF and GDNFR-α are plausible candidate genes for involvement in the pathogenesis of phaeochromocytomas. To investigate the role of GDNF in sporadic phaeochromocytomas, we scanned a panel of 22 tumors. Among these samples, only a conservative sequence variant was detected in exon 2 of GDNF. No disease-associated somatic GDNF mutations or gross gene amplification were detected in these tumors, suggesting only a minor role for GDNF in the genesis of phaeochromocytomas.

Original languageEnglish (US)
Pages (from-to)310-313
Number of pages4
JournalCancer Research
Volume57
Issue number2
StatePublished - 1997
Externally publishedYes

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor Receptors
von Hippel-Lindau Disease
Glial Cell Line-Derived Neurotrophic Factor
Pheochromocytoma
Ligands
Mutation
Multiple Endocrine Neoplasia Type 2a
Germ-Line Mutation
Genes
Exons
Neoplasms
Neurofibromatosis 1
Proto-Oncogenes
Gene Amplification
Receptor Protein-Tyrosine Kinases
Missense Mutation
Tumor Suppressor Genes
Renal Cell Carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mutation analysis of glial cell line-derived neurotrophic factor (GDNF), a ligand for the RET/GDNF receptor α complex, in sporadic phaeochromocytomas. / Dahia, Patricia L; Toledo, Sergio P A; Mulligan, Lois M.; Maher, Eamonn R.; Grossman, Ashley B.; Eng, Charis.

In: Cancer Research, Vol. 57, No. 2, 1997, p. 310-313.

Research output: Contribution to journalArticle

Dahia, Patricia L ; Toledo, Sergio P A ; Mulligan, Lois M. ; Maher, Eamonn R. ; Grossman, Ashley B. ; Eng, Charis. / Mutation analysis of glial cell line-derived neurotrophic factor (GDNF), a ligand for the RET/GDNF receptor α complex, in sporadic phaeochromocytomas. In: Cancer Research. 1997 ; Vol. 57, No. 2. pp. 310-313.
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