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Mutational load and mutational patterns in relation to age in head and neck cancer.

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is a cancer with well-defined tumor causes such as HPV infection, smoking and drinking. Using The Cancer Genome Atlas (TCGA) HNSCC cohort we systematically studied the mutational load as well as patterns related to patient age in HNSCC. To obtain a homogenous set we excluded all patients with HPV infection as well as wild type TP53. We found that the overall mutational load is higher in patients of old age. Through unsupervised hierarchical clustering, we detected distinct mutational clusters in very young as well as very old patients. In the group of old patients, we identified four enriched pathways ("Axon Guidance", "ECM-Receptor Interaction", "Focal Adhesion" and "Notch Signaling") that are only sporadically mutated in the other age groups. Our findings indicate that the four pathways regulate cell motility, tumor invasion and angiogenesis supposedly leading to less aggressive tumors in older age patients. Importantly, we did not see a strict pattern of genes always mutated in older age but rather an accumulation of mutations in the same pathways. Our study provides indications of age-dependent differences in mutational backgrounds of tumors that might be relevant for treatment approaches of HNSCCs patients.

SUBMITTER: Meucci S

PROVIDER: S-EPMC5342469 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Mutational load and mutational patterns in relation to age in head and neck cancer.

Meucci Stefano S Keilholz Ulrich U Tinhofer Ingeborg I Ebner Oliva A OA

Oncotarget 20161001 43

Head and neck squamous cell carcinoma (HNSCC) is a cancer with well-defined tumor causes such as HPV infection, smoking and drinking. Using The Cancer Genome Atlas (TCGA) HNSCC cohort we systematically studied the mutational load as well as patterns related to patient age in HNSCC. To obtain a homogenous set we excluded all patients with HPV infection as well as wild type TP53. We found that the overall mutational load is higher in patients of old age. Through unsupervised hierarchical clusterin ...[more]

PMID: 27596625

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Project description:PurposeIntensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT), two advanced modes of high-precision radiotherapy (RT), have become standard of care in the treatment of head and neck cancer. The development in RT techniques has markedly increased the complexity of target volume definition and accurate treatment delivery. The aim of this study was to indirectly investigate the quality of current TV delineation and RT delivery by analyzing the patterns of treatment failure for head and neck cancer patients in our high-volume RT center.MethodsBetween 2004 and 2014, 385 patients with pharyngeal, laryngeal, and oral cavity tumors were curatively treated with primary RT (IMRT/VMAT). We retrospectively investigated locoregional recurrences (LRR), distant metastases (DM), and overall survival (OS).ResultsMedian follow-up was 6.4 years (IQR 4.7-8.3 years) during which time 122 patients (31.7%) developed LRR (22.1%) and DM (17.7%). The estimated 2- and 5-year locoregional control was 78.2% (95% CI 73.3, 82.3) and 74.2% (95% CI 69.0, 78.8). One patient developed a local recurrence outside the high-dose volume and five patients developed a regional recurrence outside the high-dose volume. Four patients (1.0%) suffered a recurrence in the electively irradiated neck and two patients had a recurrence outside the electively irradiated neck. No marginal failures were observed. The estimated 2- and 5-year DM-free survival rates were 83.3% (95% CI 78.9, 86.9) and 80.0% (95% CI 75.2, 84.0). The estimated 2- and 5-year OS rates were 73.6% (95% CI 68.9, 77.8) and 52. 6% (95% CI 47.3, 57.6). Median OS was 5.5 years (95% CI 4.5, 6.7).ConclusionTarget volume definition and treatment delivery were performed accurately, as only few recurrences occurred outside the high-dose regions and no marginal failures were observed. Research on dose intensification and identification of high-risk subvolumes might decrease the risk of locoregional relapses. The results of this study may serve as reference data for comparison with future studies, such as dose escalation or proton therapy trials.

Dataset Information

Mutational load and mutational patterns in relation to age in head and neck cancer.

Publications

Mutational load and mutational patterns in relation to age in head and neck cancer.

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