TERT Promoter Mutations in Familial and Sporadic Melanoma
(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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https://lup.lub.lu.se/record/3577846
- author
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Science
- volume
- 339
- issue
- 6122
- pages
- 959 - 961
- publisher
- American Association for the Advancement of Science (AAAS)
- external identifiers
-
- wos:000315149600050
- scopus:84874191269
- pmid:23348503
- 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
- 2016-04-01 14:18:54
- date last changed
- 2022-04-22 02:12:42
@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 = {{American Association for the Advancement of Science (AAAS)}}, series = {{Science}}, title = {{TERT Promoter Mutations in Familial and Sporadic Melanoma}}, url = {{http://dx.doi.org/10.1126/science.1230062}}, doi = {{10.1126/science.1230062}}, volume = {{339}}, year = {{2013}}, }