TY - JOUR
T1 - Absence of activating mutations of the genes encoding the α-subunits of G11 and G(q) in thyroid neoplasia
AU - Ringel, Matthew D.
AU - Saji, Motoyasu
AU - Schwindinger, William F.
AU - Segev, Dorry
AU - Zeiger, Martha A.
AU - Levine, Michael A.
PY - 1998
Y1 - 1998
N2 - Activating mutations of the TSH receptor and α-subunit of G(s) (Gα(s)) that increase adenylyl cyclase activity have been identified in a subset of hyperfunctioning benign thyroid follicular adenomas and, less commonly, in hypofunctioning adenomas and carcinomas. In addition, some thyroid tumors exhibit inappropriate activation of phospholipase C (PLC), a signaling pathway that has been implicated in the growth and dedifferentiation of thyroid cells. We therefore hypothesized that some thyroid tumors might be caused by somatic mutations in the genes encoding the α-chain of G(q) or G11 that result in constitutive activation of the PLC pathway. We amplified regions of the α(q) and α11 genes that encode amine acids, Q209 and R183, and we screened the DNA for mutations by sequence analysis and denaturing gradient gel electrophoresis. No mutations were identified after analysis of DNA from 38 thyroid tumors and 2 poorly differentiated thyroid carcinoma cell lines, including: 13 follicular adenomas, 10 follicular carcinomas, 5 papillary carcinomas, and 10 hyperplastic nodules from multinodular goiters. We conclude that activating mutations of α(q) and α11 are absent or rare in hypofunctioning thyroid neoplasms and that other mechanisms must explain the elevated PLC activity reported in thyroid carcinoma.
AB - Activating mutations of the TSH receptor and α-subunit of G(s) (Gα(s)) that increase adenylyl cyclase activity have been identified in a subset of hyperfunctioning benign thyroid follicular adenomas and, less commonly, in hypofunctioning adenomas and carcinomas. In addition, some thyroid tumors exhibit inappropriate activation of phospholipase C (PLC), a signaling pathway that has been implicated in the growth and dedifferentiation of thyroid cells. We therefore hypothesized that some thyroid tumors might be caused by somatic mutations in the genes encoding the α-chain of G(q) or G11 that result in constitutive activation of the PLC pathway. We amplified regions of the α(q) and α11 genes that encode amine acids, Q209 and R183, and we screened the DNA for mutations by sequence analysis and denaturing gradient gel electrophoresis. No mutations were identified after analysis of DNA from 38 thyroid tumors and 2 poorly differentiated thyroid carcinoma cell lines, including: 13 follicular adenomas, 10 follicular carcinomas, 5 papillary carcinomas, and 10 hyperplastic nodules from multinodular goiters. We conclude that activating mutations of α(q) and α11 are absent or rare in hypofunctioning thyroid neoplasms and that other mechanisms must explain the elevated PLC activity reported in thyroid carcinoma.
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U2 - 10.1210/jc.83.2.554
DO - 10.1210/jc.83.2.554
M3 - Article
C2 - 9467574
AN - SCOPUS:0031764971
SN - 0021-972X
VL - 83
SP - 554
EP - 559
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -