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TERT Promoter Mutations in Familial and Sporadic Melanoma

Horn, Susanne; Figl, Adina; Rachakonda, P. Sivaramakrishna; Fischer, Christine; Sucker, Antje; Gast, Andreas; Kadel, Stephanie; Moll, Iris; Nagore, Eduardo and Hemminki, Kari LU , et al. (2013) In Science 339(6122). p.959-961
Abstract
Cutaneous melanoma occurs in both familial and sporadic forms. We investigated a melanoma-prone family through linkage analysis and high-throughput sequencing and identified a disease-segregating germline mutation in the promoter of the telomerase reverse transcriptase (TERT) gene, which encodes the catalytic subunit of telomerase. The mutation creates a new binding motif for Ets transcription factors and ternary complex factors (TCFs) near the transcription start and, in reporter gene assays, caused up to twofold increase in transcription. We then screened the TERT promoter in sporadic melanoma and observed recurrent ultraviolet signature somatic mutations in 125 of 168 (74%) of human cell lines derived from metastatic melanomas, 45 of 53... (More)
Cutaneous melanoma occurs in both familial and sporadic forms. We investigated a melanoma-prone family through linkage analysis and high-throughput sequencing and identified a disease-segregating germline mutation in the promoter of the telomerase reverse transcriptase (TERT) gene, which encodes the catalytic subunit of telomerase. The mutation creates a new binding motif for Ets transcription factors and ternary complex factors (TCFs) near the transcription start and, in reporter gene assays, caused up to twofold increase in transcription. We then screened the TERT promoter in sporadic melanoma and observed recurrent ultraviolet signature somatic mutations in 125 of 168 (74%) of human cell lines derived from metastatic melanomas, 45 of 53 corresponding metastatic tumor tissues (85%), and 25 of 77 (33%) primary melanomas. The majority of those mutations occurred at two positions in the TERT promoter and also generated binding motifs for Ets/TCF transcription factors. (Less)
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publication status
published
subject
in
Science
volume
339
issue
6122
pages
959 - 961
publisher
The American Association for the Advancement of Science
external identifiers
  • wos:000315149600050
  • scopus:84874191269
ISSN
1095-9203
DOI
10.1126/science.1230062
language
English
LU publication?
yes
id
42cc4a33-09a7-43a4-85d4-0cdf933c487f (old id 3577846)
date added to LUP
2013-04-02 07:45:03
date last changed
2019-09-17 02:41:36
@article{42cc4a33-09a7-43a4-85d4-0cdf933c487f,
  abstract     = {Cutaneous melanoma occurs in both familial and sporadic forms. We investigated a melanoma-prone family through linkage analysis and high-throughput sequencing and identified a disease-segregating germline mutation in the promoter of the telomerase reverse transcriptase (TERT) gene, which encodes the catalytic subunit of telomerase. The mutation creates a new binding motif for Ets transcription factors and ternary complex factors (TCFs) near the transcription start and, in reporter gene assays, caused up to twofold increase in transcription. We then screened the TERT promoter in sporadic melanoma and observed recurrent ultraviolet signature somatic mutations in 125 of 168 (74%) of human cell lines derived from metastatic melanomas, 45 of 53 corresponding metastatic tumor tissues (85%), and 25 of 77 (33%) primary melanomas. The majority of those mutations occurred at two positions in the TERT promoter and also generated binding motifs for Ets/TCF transcription factors.},
  author       = {Horn, Susanne and Figl, Adina and Rachakonda, P. Sivaramakrishna and Fischer, Christine and Sucker, Antje and Gast, Andreas and Kadel, Stephanie and Moll, Iris and Nagore, Eduardo and Hemminki, Kari and Schadendorf, Dirk and Kumar, Rajiv},
  issn         = {1095-9203},
  language     = {eng},
  number       = {6122},
  pages        = {959--961},
  publisher    = {The American Association for the Advancement of Science},
  series       = {Science},
  title        = {TERT Promoter Mutations in Familial and Sporadic Melanoma},
  url          = {http://dx.doi.org/10.1126/science.1230062},
  volume       = {339},
  year         = {2013},
}