TERT Promoter Mutations in Familial and Sporadic Melanoma

  title={TERT Promoter Mutations in Familial and Sporadic Melanoma},
  author={Susanne Horn and Adina Figl and Panduranga Sivaramakrishna Rachakonda and Christine Fischer and Antje Sucker and Andreas Gast and Stephanie Kadel and Iris Moll and Eduardo Nagore and Kari Hemminki and Dirk Schadendorf and Rajiv Kumar},
  pages={959 - 961}
Promoter Mutations and Cancer Cancer genome sequencing projects have highlighted the pathogenic role of recurrent mutations within the protein-coding regions of genes. Now, two studies suggest that the scope of mutations in human tumors extends to gene regulatory regions. In a study of 70 melanomas, Huang et al. (p. 957, published online 24 January) found that 71% harbored one of two specific mutations in the promoter region of TERT, the gene coding for the catalytic subunit of telomerase, the… 

Recurrent and functional regulatory mutations in breast cancer

This study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions.

Frequency of TERT promoter mutations in primary tumors of the liver

Data show that TERT promoter mutation is the most frequent genetic alteration in hepatocellular carcinoma known at this time and might become a diagnostic tool distinguishing hepatocellsular adenoma from well-differentiated hepato cellular carcinomas.

Mutations in the promoter of the telomerase gene TERT contribute to tumorigenesis by a two-step mechanism

It is shown that TPMs acquired at the transition from benign nevus to malignant melanoma do not support telomere maintenance, and data suggest that TERT promoter mutations contribute to tumorigenesis by promoting immortalization and genomic instability in two phases.

Germline TERT promoter mutations are rare in familial melanoma

Evidence is provided confirming that a rare promoter variant of TERT is associated with high penetrance, early onset melanoma and potentially other cancers, and explains <1 % of UK melanoma multicase families.

POLE mutations in families predisposed to cutaneous melanoma

Multiple cancer types in the melanoma families are observed, suggesting that some germline POLE mutations may predispose to a broad spectrum of cancers, including melanoma.

TERT promoter mutations in primary and secondary glioblastomas

The results suggest that the prognostic value of TERT mutations for poor survival is largely due to their inverse correlation with IDH1 mutations, which are a significant prognostic marker of better survival in patients with secondary glioblastomas.

Functional analysis of recurrent non-coding variants in human melanoma

Overall, this analysis prioritized several recurrent functional non-coding variants that, through downregulation of CDC20, led to perturbation of key melanoma phenotypes.

Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma

The data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies, and shows selection of a recurrent somatic synonymous mutation in cancer.

Somatic mutations in telomerase promoter counterbalance germline loss-of-function mutations

The somatic acquisition of promoter mutations in telomerase reverse transcriptase (TERT) in blood leukocytes of approximately 5% of individuals with inherited loss-of-function coding mutations in TERT or poly(A)-specific ribonuclease (PARN), another gene linked to telomere function is described.



Mutations of the BRAF gene in human cancer

BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers, with a single substitution (V599E) accounting for 80%.

BRAF mutations in metastatic melanoma: a possible association with clinical outcome.

The results confirm the high frequency of BRAF mutations in metastatic melanomas and underline the potential importance of these mutations in disease outcome and study mutations in the BRAF gene and their association with clinical parameters.

Ets2 Maintains hTERT Gene Expression and Breast Cancer Cell Proliferation by Interacting with c-Myc*

It is reported that transcription factor Ets2 is required for hTERT gene expression and breast cancer cell proliferation and co-immunoprecipitation and glutathione S-transferase pulldown assays show that ETS2 binds to the EtsA and EtsB DNA motifs on the h TERT gene promoter.

COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer

With all genomic information recently updated to GRCh37, COSMIC integrates many diverse types of mutation information and is making much closer links with Ensembl and other data resources.

elk, tissue-specific ets-related genes on chromosomes X and 14 near translocation breakpoints.

Two new members (elk-1 and elk-2) of the ets oncogene superfamily have now been identified and the possibility that rearrangements of elk loci may be involved in pathogenesis of certain tumors is suggested.

Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS

The data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma.

Melanocortin receptor 1 variants and melanoma risk: A study of 2 European populations

The data underscored the unambiguous importance of the MC1R variants towards the population burden of melanoma, however, the variants that are associated with the disease differ between the investigated populations.

Sex difference in methylation of single-copy genes in human meiotic germ cells: Implications for X chromosome inactivation, parental imprinting, and origin of CpG mutations

The observations of meiotic germ cells suggest that the female germ cells remain unmethylated, but that methylation in male germ cells occurs postnatally, prior to or during the early stages of spermatogenesis, which could provide a molecular basis for parental imprinting of the mammalian genome.