Analysis of genetic variants of frequently mutated genes in human papillomavirus-negative primary head and neck squamous cell carcinoma, resection margins, local recurrences and corresponding circulating cell-free DNA.

Background: Head and neck squamous cell carcinoma remains a substantial burden to global health. Despite evolving therapies, 5-year survival is <50% and unlike in other cancers, reliable molecular biomarkers to guide treatment do not exist.

Methods: We performed targeted panel next-generation sequencing to analyse somatic variants from primary and recurrent tumour tissue, corresponding resection margins and cell-free DNA from intra-operatively collected plasma samples from eight patients with human papillomavirus-negative head and neck squamous cell carcinoma.

Therapy-Related Transcriptional Subtypes in Matched Primary and Recurrent Head and Neck Cancer.

Purpose: The genetic relatedness between primary and recurrent head and neck squamous cell carcinomas (HNSCC) reflects the extent of heterogeneity and therapy-driven selection of tumor subpopulations. Yet, current treatment of recurrent HNSCC ignores the molecular characteristics of therapy-resistant tumor populations.

Experimental Design: From 150 tumors, 74 primary HNSCCs were RNA sequenced and 38 matched primary/recurrent tumor pairs were both whole-exome and RNA sequenced.

Local inhibition of rRNA transcription without nucleolar segregation after targeted ion irradiation of the nucleolus.

Nucleoli have attracted interest for their role as cellular stress sensors and as potential targets for cancer treatment. The effect of DNA double-strand breaks (DSBs) in nucleoli on rRNA transcription and nucleolar organisation appears to depend on the agent used to introduce DSBs, DSB frequency and the presence (or not) of DSBs outside the nucleoli. To address the controversy, we targeted nucleoli with carbon ions at the ion microbeam SNAKE.

Chromatin organization revealed by nanostructure of irradiation induced γH2AX, 53BP1 and Rad51 foci.

The spatial distribution of DSB repair factors γH2AX, 53BP1 and Rad51 in ionizing radiation induced foci (IRIF) in HeLa cells using super resolution STED nanoscopy after low and high linear energy transfer (LET) irradiation was investigated. 53BP1 and γH2AX form IRIF with same mean size of (540 ± 40) nm after high LET irradiation while the size after low LET irradiation is significantly smaller. The IRIF of both repair factors show nanostructures with partial anti-correlation.