Comprehensive Genomic Profiling of Metastatic Squamous Cell Carcinoma of the Anal Canal

Squamous cell carcinoma of the anal canal (SCCA) is a rare gastrointestinal malignancy with an increasing annual incidence globally. The majority of cases are linked to prior infection with the human papillomavirus (HPV). For patients with metastatic SCCA, no consensus standard treatment exists. Identification of relevant targeted agents as novel therapeutic approaches for metastatic SCCA has been limited by a lack of comprehensive molecular profiling. We performed whole-exome sequencing on tumor–normal pairs from 24 patients with metastatic SCCA. Tumor tissue from 17 additional patients was analyzed using a 263-gene panel as a validation cohort. Gene expression profiling was performed on available frozen tissue to assess for differential expression patterns. Based on these findings, patient-derived xenograft (PDX) models of SCCA were generated to test targeted therapies against PI3K and EGFR. Despite a low mutation burden, mutations in PIK3CA, MLL2, and MLL3 were among the most commonly mutated genes. An association between TP53 mutations and HPV-negative SCCA tumors was observed. Gene expression analysis suggested distinct tumor subpopulations harboring PIK3CA mutations and for which HPV had integrated into the host genome. In vivo studies demonstrated improvement with anti-EGFR treatment. Gene mutation frequencies, tumor mutation burden, and gene expression patterns for metastatic SCCA appear similar to other HPV-associated malignancies. Implications: This first comp...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Genomics Source Type: research

Related Links:

FRIDAY, Jan. 3, 2020 -- Only one in four patients with sinonasal squamous cell carcinoma (SNSCC) is tested for human papillomavirus (HPV), according to a study published online Dec. 30 in Cancer. Jamie R. Oliver, from the New York University School...
Source: - Pharma News - Category: Pharmaceuticals Source Type: news
This study aimed to test the role of Cx43 protein on Bcl-2 expression, tumor progression and response to taxane-based treatment in HNSCC. Human papillomavirus (HPV) negative HNSCC cell lines were tested for paclitaxel sensitivity through measuring apoptosis induction, cell viability and changes in Cx43 and Bcl-2 levels using flow cytometry, cell viability assay, immunocytochemistry and western blot. Inhibition of Cx43 expression using siRNA increased Bcl-2 protein levels in SCC25 (tongue squamous cell carcinoma) cells, while forced Cx43 expression reduced Bcl-2 levels and supported paclitaxel cytotoxicity in FaDu (hypophar...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionThis study evaluated the survival impact of HPV infection in LSCC patients. The OS of the HPV ‐positive group was better than that of the HPV‐negative group in terms of short‐term survival. Compared with the HPV‐negative group, the HPV‐positive group had a better trend of DFS, suggesting that a larger sample size and further exploration of the pathology and local control of HPV‐p ositive tumors are needed.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Abstract Acquired uniparental disomy (aUPD) leads to homozygosity facilitating identification of monoallelically expressed genes. We analyzed single-nucleotide polymorphism array-based genotyping data of 448 head and neck squamous cell carcinoma (HNSCC) samples from The Cancer Genome Atlas to determine the frequency and distribution of aUPD regions and their association with survival, as well as to gain a better understanding of their influence on the tumor genome. We used expression data from the same dataset to identify differentially expressed genes between groups with and without aUPD. Univariate and multivari...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research
CONCLUSIONS: Our results demonstrated that targeting EZH2 enhanced antigen presentation and was able to circumvent anti-PD-1 resistance. Thus, combining EZH2 targeting with anti-PD-1 may increase therapeutic susceptibility in HNSCC. PMID: 31562203 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
CONCLUSIONS.—: Anyplex II HPV28 showed a higher HPV detection rate and HPV-associated fraction than the other methods used. This assay is suitable for HPV detection in archival OPSCC tissues. PMID: 31509455 [PubMed - as supplied by publisher]
Source: Archives of Pathology and Laboratory Medicine - Category: Laboratory Medicine Authors: Tags: Arch Pathol Lab Med Source Type: research
Publication date: December 2019Source: Current Opinion in Virology, Volume 39Author(s): Jitesh B Shewale, Maura L GillisonHead and neck squamous cell carcinoma (HNSCC) is attributable to carcinogen and oncogenic virus exposure and rates are driven by the prevalence, intensity, and duration of exposures. Recent dramatic shifts in human behavior have resulted in substantial heterogeneity in HNSCC incidence trends over calendar time. For example, changes in sexual behavior during the 1900s likely increased exposure to oral human papillomavirus (HPV) infection and, consequently, rates of HPV-positive HNSCC. Shifting rate-ratio...
Source: Current Opinion in Virology - Category: Virology Source Type: research
ConclusionsResidual disease may be inconspicuous or absent on cytology, colposcopy and/or histology. Management taking account of risk of recurrence (age, CIN3 depth, incomplete initial excision) could avoid some post-treatment cancers.
Source: Journal of the American Society of Cytopathology - Category: Cytology Source Type: research
Alla S. Koltsova1,2, Anna A. Pendina1, Olga A. Efimova1*, Olga G. Chiryaeva1, Tatyana V. Kuznetzova1 and Vladislav S. Baranov1,2 1D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia 2Department of Genetics and Biotechnology, Saint Petersburg State University, Saint Petersburg, Russia In the present review, we focus on the phenomenon of chromothripsis, a new type of complex chromosomal rearrangements. We discuss the challenges of chromothripsis detection and its distinction from other chromoanagenesis events. Along with already known causes and mechanisms, we introdu...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
We report a case of misdiagnosed endometrial cancer by D&C, but with a positive cytopathological finding. Following that, a meta-analysis including 4,179 patients of endometrial diseases with cyto-histopathological results was performed to assess the value of the endometrial cytological method in endometrial cancer diagnosis. The pooled sensitivity and specificity of the cytological method in detecting endometrial atypical hyperplasia or cancer was 0.91[95% confidence interval (CI) 0.74–0.97] and 0.96 (95% CI 0.90–0.99), respectively. The pooled positive likelihood ratio and negative likelihood ratio was 25.4 (...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Gastroenterology | Genetics | Genital Warts | HPV Testing | Human Papillomavirus (HPV) | Skin Cancer | Squamous Cell Carcinoma | Study