Abstract
Genomic deoxyribonucleic acid from surgical specimens of 25 pituitary adenomas was screened for the presence of mutations in the tumor suppressor gene, retinoblastoma gene, using polymerase chain reaction and single-strand conformation polymorphism analysis, followed by direct deoxyribonucleic acid sequencing. Mutation causing an amino acid change was found in one of the 25 pituitary adenomas. The mutation site was in exon 19 (codon 621) of the retinoblastoma gene. In addition, there were three types of silent mutations in introns of the gene. The patient in whom the retinoblastoma mutation was identified had a tumor with high clinical malignancy, a high percentage of c-myc protein-labeled cells, and a diagnosis of plurihormonal pituitary adenoma based on the presence of cells immunoreactive for five pituitary hormones. This article suggests that point mutation of retinoblastoma gene is rare in human pituitary adenomas but may provide a marker for aggressive pituitary adenoma.
Similar content being viewed by others
References
Alexander JM, Biller BMK, Bikkal H, Arnold A, Klibanski A. A clinically non-functioning pituitary tumors are monoclinal in origin. J Clin Invest 86:336–340, 1990.
Gicquel, C, Bouc YL, Luton JP, Girard F, Bertagna X. Monoclonality of corticotroph macroadenomas in Cushing's disease. J Clin Endocrinol Metab 75:472–475, 1992.
Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S. Clonal origin of pituitary adenomas. J Clin Endocrinol Metab 71:1427–1433, 1990.
Jacks T, Fazeli A, Schmitt EM, Bronson RT, Goodell MA, Weinberg RA. Effects of an Rb mutation in the mouse. Nature 359:295–300, 1992.
Ikeda H, Yoshimoto T. The relationship between c-myc protein expression, the bromodeoxyuridine labeling index and the biological behavior of pituitary adenomas. Acta Neuropathol 83:361–364, 1992.
Rustigi AK, Dyson N, Bernards R. Aminoterminal domains of c-myc and N-myc proteins mediate binding to the retinoblastoma gene product. Nature 352:541–544, 1991.
Horowitz JM, Yandell DW, Park SH, Canning S, Whyte P, Buchkovich K, Harlow E, Weinberg RA, Dryia T. Point mutational inactivation of the retinoblastoma antioncogene. Science 243:937–940, 1989.
Cryns VL, Alexander JM, Klibanski A, Arnold A. The retinoblastoma gene in human pituitary tumors. J Clin Endocrinol Metab 77:644–646, 1993.
Woloschak M, Roberts JL, Post KD. Loss of heterozygosity at the retinoblastoma locus in human pituitary tumors. Cancer 74:693–696, 1994.
Zhu, J, Leon SP, Beggs AH, Busque L, Gilliland DG, Black PM. Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus. J Clin Endocrinol Metab 78:922–927, 1994.
McGee TL, Yandell DW, Dryja TP. Structure and partial genomic sequence of the human retinoblastoma susceptibility gene. Gene 80:119–128, 1989.
Yandell DW, Draja TP. Detection of DNA sequence polymorphisms by enzymatic amplification and direct genomic sequencing. Am J Hum Genet 45:547–555, 1989.
Landis CA, Masters SB, Spada A, Pace AW, Bourne HR, Vallar L. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumors. Nature 340:692–696, 1989.
Lyons J, Landis CA, Harsh G, Vallar L, Grunewald K, Feichtinger H, Duh QY, Clark OH, Kawasaki E, Bourne HR, McComick F. Two G protein oncogenesis in human endocrine tumors. Science 249:655–659, 1990.
Karga HJ, Alexander JM, Hedley-Whyte ET, Klibanski A, Jameson JL. Ras mutations in pituitary tumors. J Clin Endocrinol Metab 74:914–919, 1992.
Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323:643–646, 1986.
Hansen MF, Koufos A, Gallie BL, Phillips RA, Fodstad O, Brogger A, GeddeDahl T, Cavenee WK. Osteosarcoma and retinoblastoma: a shared chromosomal mechanism revealing recessive predisposition. Proc Natl Acad Sci USA 82:6216–6220, 1985.
Friend SH, Horowitz JM, Gerber MR, Wang X, Bogenmann E, Li FP, Weinberg RA. Deletions of a DNA sequence in retinoblastomas and mesenchymal tumors: organization of the sequence and its encoded protein. Proc Natl Acad Sci USA 84:9059–9063, 1987.
Harbour JW, Lai S-L, Whang-Peng J, Gazdar AF, Minna JD, Kaye FJ. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science 241:353–357, 1988.
Lee EYHP, To H, Shew JY, Bookstein R, Scully P, Lee WH. Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science 241:218–221, 1988.
T'Ang A, Valey JM, Chakraborty S, Murphree AL, Fung YKT. Structural rearrangement of the retinoblastoma gene in human breast carcinoma. Science 242:263–266, 1988.
Ikeda H, Suzuki J, Sasano N, Niizuma H. The development and morphogenesis of the human pituitary gland. Anat Embryol (Berl) 178:327–336, 1988.
Ikeda H, Yoshimoto T. Developmental changes in proliferative activity of cells of the murine Rathke's pouch. Cell Tissue Res 263:41–47, 1991.
Ikeda H, Yoshimoto T, Yandell DW. Hormone production and c-myc protein labeling in plurihormonal adenomas. Endocr Pathol 5:162–168, 1994.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ikeda, H., Beauchamp, R.L., Yoshimoto, T. et al. Detection of heterozygous mutation in the retinoblastoma gene in a human pituitary adenoma using PCR-SSCP analysis and direct sequencing. Endocr Pathol 6, 189–196 (1995). https://doi.org/10.1007/BF02739882
Issue Date:
DOI: https://doi.org/10.1007/BF02739882