Whole-Exome Sequencing of HPV Positive Tonsillar and Base of Tongue Squamous Cell Carcinomas Reveals a Global Mutational Pattern along with Relapse-Specific Somatic Variants

To identify predictive/targetable markers in human papillomavirus positive (HPV+) tonsillar and base of tongue cancer (TSCC/BOTSCC), whole-exome sequencing (WES) of tumours of patients with/without recurrence was performed. Forty primary tumours and adjacent normal tissue were separated by micro-dissection from formalin-fixed paraffin-embedded tissue from patients treated with curative intent 2000–2014 at Karolinska University Hospital. Successful sequencing was obtained in primary tumours of 18 patients without and primaries of 17 with local or distant recurrence, as well as in 10 corresponding recurrences (i.e., five local relapses and five distant metastases) from these 17 patients. One variant—a high-impact deletion in the CDC27 gene—was observed only in primaries of 5/17 patients that had a recurrence after full treatment but in none of those without recurrence. In addition, 3 variants and 26 mutated genes, including CDC27, BCLAF1 and AQP7, were present in at least 30% of all primary tumours independent of prognosis. To conclude, a CDC27 deletion was specific and found in ~30% of samples from patients with a local relapse/distant metastasis and could, therefore, potentially be a prospective marker to predict prognosis. Commonly mutated genes, such as BCLAF1, should be further studied in the context of targeted therapy.

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The Potential of Whole-Exome Sequencing (WES) in Neuropediatric Patients: Single-Center Experience at the University Hospital Hamburg Eppendorf

Neuropediatrics ◽

10.1055/s-0037-1602920 ◽

2017 ◽

Vol 48 (S 01) ◽

pp. S1-S45

Author(s):

J. Denecke ◽

J. Johannsen ◽

A. Neu ◽

R. Santer ◽

K. Kloth ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

University Hospital ◽

Single Center ◽

Single Center Experience ◽

Whole Exome ◽

The University

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Clinical and genetic profiling of nevoid basal cell carcinoma syndrome in Korean patients by whole-exome sequencing

Scientific Reports ◽

10.1038/s41598-020-80867-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Boram Kim ◽

Man Jin Kim ◽

Keunyoung Hur ◽

Seong Jin Jo ◽

Jung Min Ko ◽

...

Keyword(s):

Basal Cell Carcinoma ◽

Cell Carcinoma ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Basal Cell ◽

University Hospital ◽

Genetic Profiling ◽

Korean Patients ◽

Pathogenic Variants ◽

Whole Exome

AbstractNevoid basal cell carcinoma syndrome (NBCCS) is mainly characterised by multiple basal cell carcinomas (BCCs) caused by PTCH1, PTCH2, and SUFU. However, clinical and genetic data on Asian NBCCS patients are limited. We aimed to analyse the clinical phenotypes and genetic spectrum of Korean patients with NBCCS. Fifteen patients with NBCCS at Seoul National University Hospital were included, and their clinical data were analysed. Whole-exome sequencing and/or multiplex ligation-dependent probe amplification using peripheral blood were performed to identify genetic causes. Genetic analysis revealed that 73.3% (11/15) of the patients carried 9 pathogenic variants, only in the PTCH1 gene. Variants of uncertain significance (VUS) and likely benign were also detected in 2 (13.3%) and 2 (13.3%) patients, respectively. BCCs were found in the majority of the cases (93.3%) and the number of BCCs increased with age (ρ = 0.595, P = 0.019). This study revealed that PTCH1 pathogenic variants were the main cause of NBCCS in Korean patients. As BCCs are commonly detected, a periodic dermatologic examination is recommended. Finally, our results support the addition of genetic screening to the existing criteria for NBCCS diagnosis.

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Patterns of Whole Exome Sequencing in Resected Cholangiocarcinoma

Cancers ◽

10.3390/cancers13164062 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4062

Author(s):

Lucas W. Thornblade ◽

Paul Wong ◽

Daneng Li ◽

Susanne G. Warner ◽

Sue Chang ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Targeted Therapies ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Sequencing Data ◽

Curative Intent ◽

Genetic Profiling ◽

Whole Exome ◽

Future Care

Background: With minimally effective chemotherapy options, cholangiocarcinoma patients have 5 year survival rate of 10%. Tumor genetic profiling (TGP) can identify mutations susceptible to targeted therapies. We sought to describe the use of TGP and frequency of actionable results in resected cholangiocarcinoma. Methods: A retrospective review of patients undergoing curative intent resection at a comprehensive cancer center (2010–2020). Clinicopathologic and partial or whole exome sequencing data were reviewed. Results: 114 patients (mean age 65 ± 11 years, 45% female) underwent resection of cholangiocarcinoma (46% poorly differentiated, 54% intrahepatic, 36% node positive, 75% margin negative). Additionally, 32% of patients underwent TGP, yielding a mean of 3.1 actionable mutations per patient (range 0–14). Mutations aligned with a median of one drug per patient (range 0–11). Common mutations included TP53 (33%), KRAS (31%), IDH1/2 (14%), FGFR (14%), and BRAF (8%). Targeted therapies were administered in only 4% of patients (23% of eligible sequenced patients). After a median 22 months, 23% had recurrence and 29% were deceased. Discussion: TGP for cholangiocarcinoma has increased over the last decade with targeted therapies identified in most sequenced tumors, impacting treatment in a quarter of eligible patients. Precision medicine will play a central role in the future care of cholangiocarcinoma.

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Longitudinal whole-exome sequencing of cell-free DNA unravels the metastatic evolutionary dynamics of BRCA2-mutated breast cancer

10.1101/2020.01.10.901330 ◽

2020 ◽

Author(s):

R.K Hastings ◽

M.R Openshaw ◽

M Vazquez ◽

AB Moreno-Cardenas ◽

D Fernandez-Garcia ◽

...

Keyword(s):

Breast Cancer ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Evolutionary Dynamics ◽

Immune Escape ◽

Local Relapse ◽

Evolutionary Trajectory ◽

Whole Exome ◽

Stage Disease ◽

First Time

AbstractLittle is known about the metastatic evolutionary dynamics of BRCA2-mutated cancers. Here, we applied whole-exome sequencing (WES) of primary tumor (PT), local relapse (LR) and eight serial plasma cfDNA samples collected from disease progression to depict the 12 years evolutionary trajectory of a metastatic BRCA2-mutated breast cancer. While longitudinal WES-cfDNA recapitulated clonal and subclonal mutations and copy number profiles detected in LR, emergence of plasma-exclusive mutations in TSC2 and HDAC9 cancer-related genes and loss of HLA loci as an immune escape mechanism were also detected. Lastly, mutation signature 3, associated with homologous recombination deficiency and response to platinum-based therapy raised profoundly from 19% in PT to 60% in late stage disease. In conclusion, we show for the first time that longitudinal WES-cfDNA enables the evolutionary trajectory of advanced cancer to be uncovered and that increment of MS3 and loss of HLA are key players in this BRCA2-mutated breast metastasis.

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