FIRST CONTINUOUS HUMAN PHEOCHROMOCYTOMA CELL-LINE - KNA - BIOLOGICAL,CYTOGENETIC AND MOLECULAR CHARACTERIZATION OF KNA CELLS

Pheochromocytomas are rare rumours, with an incidence of 1-2 per milli on which arise from chromaffin cells of the adrenal medulla. They occu r sporadically or as part of dominantly inherited cancer syndromes lik e 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 spo radic pheochromocytoma of the right adrenal gland of a 73-year-old wom an. The KNA cells grow as suspensions of spheroids and show the morpho logical and immunocytochemical characteristics of neuronal chromaffin cells, such as neuroendocrine granules, and positive reactions to chro mogranin-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 dipl oid (46,XX, n = 50) to hypodiploid (43-45,XX, n = 15) karyotype. In hy podiploid metaphases most frequently #19, #17, #21 and #22 were missin g. Chromosome arms Ip 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 continu ous pheochromocytoma cell line available. KNA represents the first rep ort on a human continuous pheochromocytoma cell line, the first report of structural chromosome aberrations in pheochromocytomas and the fir st report of a RET mutation TGC to TGG in exon 10 of the RET proto-onc ogene in a sporadic pheochromocytoma. (C) 1998 Chapman and Hall.