hTR repressor-related gene on human chromosome 10p15.1.
Somatic cells express genes that suppress telomerase activity and these genes may be inactivated in tumour cells. We postulated that cancer cells acquire immortality by activation of telomerase by the loss of such a gene. We have reported recently that a telomerase repressor gene may be located on 10p15.1 by deletion mapping using microcell-mediated chromosome transfer (MMCT), radiated microcell fusion (RMF), fluorescent in situ hybridization (FISH) and STS analysis. To independently confirm this result, we correlated expression of RNA component of telomerase (hTR) as a marker of telomerase expression by in situ hybridization with allelic loss in pulmonary carcinoid tumours. Unlike most malignant tumours, pulmonary carcinoids (which are low-grade malignant tumours) are heterogeneous for telomerase expression. Loss of 5 closely spaced polymorphic markers on 10p15.1, especially D10S1728, were highly correlated with hTR expression. In an additional experiment, 10p15.1 showed higher and more significant correlation than any region of 3p where it has been predicted as another chromosomal location of telomerase repressor with allelic loss of the region. Our findings strongly suggest that 10p15.1 harbours a gene involved in repression of telomerase RNA component in human somatic cells and each putative repressor (on 3p and 10p) may act independently.
Miura
N
N
Hamon Center for Therapeutic Oncology Research, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8593, USA.
Onuki
N
N
Rathi
A
A
Virmani
A
A
Nakamoto
S
S
Kishimoto
Y
Y
Murawaki
Y
Y
Kawasaki
H
H
Hasegawa
J
J
Oshimura
M
M
Travis
W D
WD
Gazdar
A F
AF
D002276:Carcinoid Tumor / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D017403:In Situ Hybridization; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D012313:RNA; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm / Q000032:analysis; D022661:RNA, Untranslated / Q000096:biosynthesis / Q000235:genetics*; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics*
D005819:Genetic Markers; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm; D022661:RNA, Untranslated; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase