First continuous human pheochromocytoma cell line: KNA. Biological, cytogenetic and molecular characterization of KNA cells.
Pheochromocytomas are rare tumours, with an incidence of 1-2 per million which arise from chromaffin cells of the adrenal medulla. They occur sporadically or as part of dominantly inherited cancer syndromes like multiple endocrine neoplasia 2 (MEN2A and 2B) and others. Continuous cell lines, not available so far, are essential tools for studies in these tumours. A continuous cell line (KNA) was established from a sporadic pheochromocytoma of the right adrenal gland of a 73-year-old woman. The KNA cells grow as suspensions of spheroids and show the morphological and immunocytochemical characteristics of neuronal chromaffin cells, such as neuroendocrine granules, and positive reactions to chromogranin- and related peptide-, neuron specific enolase and vasoactive intestinal peptide antibodies. Neurite-like processes are formed after addition of nerve growth factor. Chromosomal analyses revealed a diploid (46,XX,n = 50) to hypodiploid (43-45,XX,n = 15) karyotype. In hypodiploid metaphases most frequently #19, #17, #21 and #22 were missing. Chromosome arms 1p and 4q showed apparently consistent interstitial deletions: 6q, 8q, 13q and 22q showed clonal interstitial deletions. The cell line shows a heterozygous sequence variant TGC (cysteine) to TGG (tryptophan) in codon 611 in exon 10 of the RET proto-oncogene. So far, PC-12, a rat adrenal pheochromocytoma, has been the only continuous pheochromocytoma cell line available. KNA represents the first report on a human continuous pheochromocytoma cell line, the first report of structural chromosome aberrations in pheochromocytomas and the first report of a RET mutation TGC to TGG in exon 10 of the RET proto-oncogene in a sporadic pheochromocytoma.
Pfragner
R
R
Department of General and Experimental Pathology, Medical School, University of Graz, Austria.
Behmel
A
A
Smith
D P
DP
Ponder
B A
BA
Wirnsberger
G
G
Rinner
I
I
Porta
S
S
Henn
T
T
Niederle
B
B
D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D019943:Amino Acid Substitution; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002395:Catecholamines / Q000032:analysis; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis; D002869:Chromosome Aberrations; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000648:ultrastructure; D004299:Dopamine beta-Hydroxylase / Q000032:analysis; D029721:Drosophila Proteins; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics; D009368:Neoplasm Transplantation; D020932:Nerve Growth Factor / Q000494:pharmacology; D009479:Neuropeptides / Q000032:analysis; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011003:Ploidies; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000637:transplantation / Q000648:ultrastructure
D014408:Biomarkers, Tumor; D002395:Catecholamines; D053379:Chromogranin A; D002864:Chromogranins; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D009479:Neuropeptides; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020932:Nerve Growth Factor; D004299:Dopamine beta-Hydroxylase; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse