Analysis of PTEN mutation in non-familial pheochromocytoma.
PTEN, a tumor suppressor gene, is frequently mutated in a variety of human tumors. In mice, monoallelic inactivation of this gene predisposes animals to neoplasia of multiple organs. Interestingly, Pten heterozygous mice develop bilateral hyperplasia of the adrenal medulla. In this report we demonstrate that these neoplasms are hormonally active pheochromocytomas that secrete increased amounts of bioactive catecholamines: norepinephrine and epinephrine. To test a possibility that PTEN might be one of the genes responsible for human sporadic pheochromocytoma, we performed mutation analysis of DNA obtained from tumors of 29 patients. However, direct sequencing of all nine exons of the PTEN gene, including the splice junctions, revealed no mutations. Examination of protein expression by immunohistochemistry using 8 normal adrenals and 11 sporadic pheochromocytomas showed no decrease in the PTEN protein expression in the tumor tissue, but upregulation of insulin-like growth factor II, a peptide implicated in growth of adrenal tissue, was observed in four cases (36%).
Puc
Janusz
J
Institute for Cancer Genetics, Columbia University, New York, NY 10032, USA. jpuc@ucsd.edu
Placha
Grzegorz
G
Wocial
Bozenna
B
Podsypanina
Katrina
K
Parsons
Ramon
R
Gaciong
Zbigniew
Z
D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D007150:Immunohistochemistry; D051379:Mice; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010673:Pheochromocytoma / Q000235:genetics*
D017931:DNA Primers; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse