TY - JOUR
T1 - The Molecular Biology of Medullary Thyroid Carcinoma
T2 - A Model for Cancer Development and Progression
AU - Nelkin, Barry D.
AU - Bustros, Andrée C.
AU - Mabry, Mack
AU - Baylin, Stephen B.
PY - 1989/6/2
Y1 - 1989/6/2
N2 - Medullary thyroid carcinoma (MTC) is an important human cancer for the study of molecular abnormalities that underlie initiation of neoplasia and subsequent cellular changes during tumor progression. This tumor can occur in different inherited forms, each mediated by autosomal dominant genetic events. Germline abnormalities on chromosome 10 are linked to at least one type of genetic MTC, multiple endocrine neoplasia type II. Our studies of chromosome 10 in DNA from MTC tumors failed to detect frequent loss of polymorphic DNA markers, suggesting that the genetic mechanisms involved in MTC development may be different from those for other inherited cancers such as retinoblastoma. During tumor progression of MTC, abnormalities develop in expression of the mature phenotype of the endocrine cell from which the tumor arises. In cell culture, chemical modulation or gene insertion can lead to partial correction of these defects in differentiation capacity by activating cellular signaling processes. These studies offer opportunities to dissect the molecular events that regulate endocrine cell differentiation, to determine the precise abnormalities that may underlie the initiation and tumor progression events in MTC and related cancers, and, thereby, to identify new targets for therapeutic intervention.
AB - Medullary thyroid carcinoma (MTC) is an important human cancer for the study of molecular abnormalities that underlie initiation of neoplasia and subsequent cellular changes during tumor progression. This tumor can occur in different inherited forms, each mediated by autosomal dominant genetic events. Germline abnormalities on chromosome 10 are linked to at least one type of genetic MTC, multiple endocrine neoplasia type II. Our studies of chromosome 10 in DNA from MTC tumors failed to detect frequent loss of polymorphic DNA markers, suggesting that the genetic mechanisms involved in MTC development may be different from those for other inherited cancers such as retinoblastoma. During tumor progression of MTC, abnormalities develop in expression of the mature phenotype of the endocrine cell from which the tumor arises. In cell culture, chemical modulation or gene insertion can lead to partial correction of these defects in differentiation capacity by activating cellular signaling processes. These studies offer opportunities to dissect the molecular events that regulate endocrine cell differentiation, to determine the precise abnormalities that may underlie the initiation and tumor progression events in MTC and related cancers, and, thereby, to identify new targets for therapeutic intervention.
UR - http://www.scopus.com/inward/record.url?scp=0024588674&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024588674&partnerID=8YFLogxK
U2 - 10.1001/jama.1989.03420210078020
DO - 10.1001/jama.1989.03420210078020
M3 - Article
C2 - 2654432
AN - SCOPUS:0024588674
SN - 0098-7484
VL - 261
SP - 3130
EP - 3135
JO - JAMA: The Journal of the American Medical Association
JF - JAMA: The Journal of the American Medical Association
IS - 21
ER -