Promoter region mutations of the telomerase reverse transcriptase (TERT) gene in head and neck squamous cell carcinoma

Yılmaz, İsmail; Erkul, Evren; Sarı, Serkan; Issın, Gizem; Tural, Ersin; Terzi, Neslihan Terzi Kaya; Karatay, Hüseyin; Çelık, Mehmet; Ulusan, Murat; Bılgıç, Bilge

doi:10.1016/j.oooo.2020.02.015

Cited by 14 publications

(22 citation statements)

References 19 publications

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“…In our cohort, we found 31.3% (45 of 144) of OCSCC samples harboured TERT promoter mutations, which was in line with other studies ( 13 , 28 , 30 , 33 , 34 ). In agreement with other studies on OCSCC ( 20 , 28 – 32 ), the two mutations have different frequency, with a higher prevalence of -124 C>T (29 of 144) compared to -146 C>T (16 of 144).…”

Section: Discussionsupporting

confidence: 92%

“…In the literature, the frequency of TERT promoter mutations in OCSCC varies significantly among studies ranging from 30.4 to 75% (13,(28)(29)(30)(31)(32)(33)(34). This variability could be attributable to different patient population characteristics or methodological approaches.…”

Section: Discussionmentioning

confidence: 99%

“…Corroborating our results, Arantes et al (33) found that the -124 C>T TERT promoter mutation was associated with increased risk of tumour relapse and death in a cohort of 88 Brazilian patients with SCC of the UADT. However, other studies in different tumour types have reported contradicting clinical effects of TERT promoter mutations, ranging from poorer survival associated with the -146 C>T TERT promoter mutation to unchanged clinical outcome (28,29,32,(51)(52)(53)(54). Given that the two mutations create an identical sequence corresponding to a de novo binding site for ETS transcription factors, these alternative results may depend on the genetic context, including the SNP background in which TERT mutations arise.…”

Section: Discussionmentioning

confidence: 99%

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TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma

et al. 2021

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ObjectiveTo date, no useful prognostic biomarker exists for patients with oral squamous cell carcinoma (OCSCC), a tumour with uncertain biological behaviour and subsequent unpredictable clinical course. We aim to investigate the prognostic significance of two recurrent somatic mutations (-124 C>T and -146 C>T) within the promoter of telomerase reverse transcriptase (TERT) gene and the impact of TERT single nucleotide polymorphism (SNP) rs2853669 in patients surgically treated for OCSCC.MethodsThe genetic frequencies of rs2853669, -124 C>T and -146 C>T as well as the telomere length were investigated in 144 tumours and 57 normal adjacent mucosal (AM) specimens from OCSCC patients.ResultsForty-five tumours harboured TERT promoter mutations (31.3%), with -124 C>T and -146 C>T accounting for 64.4% and 35.6% of the alterations respectively. Patients with -124 C>T TERT promoter mutated tumours had the shortest telomeres in the AM (p=0.016) and showed higher risk of local recurrence (hazard ratio [HR]:2.75, p=0.0143), death (HR:2.71, p=0.0079) and disease progression (HR:2.71, p=0.0024) with the effect being potentiated by the co-occurrence of T/T genotype of rs2853669.Conclusion-124 C>T TERT promoter mutation as well as the T/T genotype of the rs2853669 SNP are attractive independent prognostic biomarkers in patients surgically treated for OCSCC, with the coexistence of these genetic variants showing a synergistic impact on the aggressiveness of the disease.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma

et al. 2021

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“…We have detected pTERT mutations in 6.4% (3/47) of patients, all originating from larynx (Figure 1). Recent reports indicate that pTERT mutations are typically found in oral cancers (up to more than 50%) and rare or absent in other sites [64][65][66], therefore our results again reaffirm these findings. Consequently, pTERT mutations seem to be also very rare in esophageal squamous cell carcinoma [67].…”

Section: Discussionsupporting

confidence: 90%

Analysis of Mutational Profile of Hypopharyngeal and Laryngeal Head and Neck Cancers Identifies KMT2C as a Potential Tumor Suppressor

Machnicki

Rzepakowska

Janowska

et al. 2021

Preprint

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Hypopharyngeal cancer represents one of worst types of head and neck tumors with only few studies focusing on the genomic profile of this type of cancer. Using targeted next-generation sequencing we analyzed 48 HPV-negative tumor samples including 23 originating from hypopharynx, and 25 from larynx. Among genes previously described as significantly mutated, TP53, FAT1, NOTCH1, KMT2C and CDKN2A were found to be most frequently mutated. We also found that more than three-fourths of our patients harbored candidate ac-tionable or prognostic alterations in genes belonging to RTK/ERK/PI3K, cell-cycle and DNA-damage repair pathways. Using previously published data we compared 67 hypopharyngeal cancers to 595 head and neck cancers from other sites and found no prominent differences in mutational frequency except for CASP8 and HRAS genes. Since we observed relatively frequent mutations of KTM2C (MLL3) in our dataset, we analyzed their role in vitro by generating KMT2C-mutant hypopharyngeal cancer cell line FaDu with CRISPR-Cas9. We demonstrate that KMT2C loss-of-function results in increased colony formation and proliferation, in concordance with its previously published results. In summary, our results show that mutational profile of hypopharyngeal cancers might be similar to the one observed for other head and neck cancers with respect to minor differences and includes multiple candidate actionable and prognostic genetic alterations. We also demonstrate for the first time that KMT2C gene may play a role of tumor suppressor in head and neck cancer, which opens new possibilities in the search for new targeted treatment approaches.

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“…Due to the latter, these cells exhibit short telomeres and chromosomal instability[ 29 ]. Somatic mutations in the telomerase gene promoter have been described in gliomas[ 30 ], head and neck cancer[ 31 ], thyroid carcinoma[ 32 ], hepatocellular carcinoma[ 33 ], squamous cell carcinoma[ 34 ], bladder cancer[ 35 ], breast carcinoma[ 36 ] and melanomas[ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Breast cancer: Muscarinic receptors as new targets for tumor therapy

Español¹,

Salem²,

Sanchez³

et al. 2021

WJCO

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The development of breast cancer is a complex process that involves the participation of different factors. Several authors have demonstrated the overexpression of muscarinic acetylcholine receptors (mAChRs) in different tumor tissues and their role in the modulation of tumor biology, positioning them as therapeutic targets in cancer. The conventional treatment for breast cancer involves surgery, radiotherapy, and/or chemotherapy. The latter presents disadvantages such as limited specificity, the appearance of resistance to treatment and other side effects. To prevent these side effects, several schedules of drug administration, like metronomic therapy, have been developed. Metronomic therapy is a type of chemotherapy in which one or more drugs are administered at low concentrations repetitively. Recently, two chemotherapeutic agents usually used to treat breast cancer have been considered able to activate mAChRs. The combination of low concentrations of these chemotherapeutic agents with muscarinic agonists could be a useful option to be applied in breast cancer treatment, since this combination not only reduces tumor cell survival without affecting normal cells, but also decreases pathological neo-angiogenesis, the expression of drug extrusion proteins and the cancer stem cell fraction. In this review, we focus on the previous evidences that have positioned mAChRs as relevant therapeutic targets in breast cancer and analyze the effects of administering muscarinic agonists in combination with conventional chemotherapeutic agents in a metronomic schedule.

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Promoter region mutations of the telomerase reverse transcriptase (TERT) gene in head and neck squamous cell carcinoma

Cited by 14 publications

References 19 publications

TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma

TERT Promoter Mutations and rs2853669 Polymorphism: Useful Markers for Clinical Outcome Stratification of Patients With Oral Cavity Squamous Cell Carcinoma

Analysis of Mutational Profile of Hypopharyngeal and Laryngeal Head and Neck Cancers Identifies KMT2C as a Potential Tumor Suppressor

Breast cancer: Muscarinic receptors as new targets for tumor therapy

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