scholarly journals Description of the genetic variants identified in a cohort of patients diagnosed with localized anal squamous cell carcinoma and treated with panitumumab

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lucía Trilla-Fuertes ◽  
Angelo Gámez-Pozo ◽  
Joan Maurel ◽  
Rocio Garcia-Carbonero ◽  
Jaume Capdevila ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Practice ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Variants ◽  
Anal Carcinoma ◽  
Genetic Alterations ◽  
Daily Clinical Practice ◽  
Complete Regression ◽  
Anal Squamous Cell Carcinoma

AbstractSquamous cell carcinoma is the most frequent histologic type of anal carcinoma. The standard of care since the 1970s has been a combination of 5-fluorouracil, mitomycin C, and radiotherapy. This treatment is very effective in T1/T2 tumors (achieving complete regression in 80–90% of tumors). However, in T3/T4 tumors, the 3-year relapse free survival rate is only 50%. The VITAL trial aimed to assess the efficacy and safety of panitumumab in combination with this standard treatment. In this study, 27 paraffin-embedded samples from the VITAL trial and 18 samples from patients from daily clinical practice were analyzed by whole-exome sequencing and the influence of the presence of genetic variants in the response to panitumumab was studied. Having a moderate- or high-impact genetic variant in PIK3CA seemed to be related to the response to panitumumab. Furthermore, copy number variants in FGFR3, GRB2 and JAK1 were also related to the response to panitumumab. These genetic alterations have also been studied in the cohort of patients from daily clinical practice (not treated with panitumumab) and they did not have a predictive value. Therefore, in this study, a collection of genetic alterations related to the response with panitumumab was described. These results could be useful for patient stratification in new anti-EGFR clinical trials.

scholarly journals Mutational profile of non-metastatic anal squamous cell carcinoma: a restrictive high impact genetic variants analysis

2019 ◽  
Vol 30 ◽  
pp. iv113
Author(s):  
L. Trilla ◽  
I. Ghanem ◽  
A. Gámez ◽  
J. Maurel ◽  
À Campos-Barros ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Variants ◽  
High Impact ◽  
Anal Squamous Cell Carcinoma

scholarly journals Comprehensive characterization of the mutational landscape in localized anal squamous cell carcinoma

2019 ◽  
Author(s):  
Lucía Trilla-Fuertes ◽  
Ismael Ghanem ◽  
Joan Maurel ◽  
Laura G-Pastrián ◽  
Marta Mendiola ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Variants ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
High Impact ◽  
Clinical Samples ◽  
Anal Squamous Cell Carcinoma

AbstractPurposeAnal squamous cell carcinoma (ASCC) is a rare neoplasm. Chemo-radiotherapy is the standard of care, with no therapeutic advances achieved over the past three decades. Thus, a deeper molecular characterization of this disease is still necessary.MethodsWe analyzed 46 paraffin-embedded tumor samples from patients diagnosed with primary ASCC by exome sequencing. A bioinformatics approach focused in the identification of high impact genetic variants, which may act as drivers of oncogenesis, was performed. The relation between genetics variant and prognosis was also studied.ResultsThe list of high impact genetic variants was unique for each patient. However, the pathways in which these genes are involved are well-known hallmarks of cancer, such as angiogenesis or immune pathways. Additionally, we determined that genetic variants in BRCA2, ZNF750, FAM208B, ZNF599 and ZC3H13 genes are related with poor disease-free survival in ASCC.ConclusionHigh impact genetic variants in ASCC affect pathways involved in cancer development, and may play a role in the etiology of the disease. Variants in BRCA2, ZNF750, FAM208B, ZNF599 and ZC3H13 genes seem to be related with prognosis in ASCC. Sequencing of ASCC clinical samples appears an encouraging tool for the molecular portrait of this disease.

scholarly journals New Therapeutic Opportunities for the Treatment of Squamous Cell Carcinomas: A Focus on Novel Driver Kinases

2021 ◽  
Vol 22 (6) ◽  
pp. 2831
Author(s):  
Ryan Bensen ◽  
John Brognard
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Fate ◽  
Squamous Cell ◽  
Copy Number Gain ◽  
Genetic Alterations ◽  
Distal Portion ◽  
Squamous Cell Carcinomas ◽  
Cell Fate Decisions ◽  
Genetic Landscape

Squamous cell carcinomas of the lung, head and neck, esophagus, and cervix account for more than two million cases of cancer per year worldwide with very few targetable therapies available and minimal clinical improvement in the past three decades. Although these carcinomas are differentiated anatomically, their genetic landscape shares numerous common genetic alterations. Amplification of the third chromosome’s distal portion (3q) is a distinguishing genetic alteration in most of these carcinomas and leads to copy-number gain and amplification of numerous oncogenic proteins. This area of the chromosome harbors known oncogenes involved in squamous cell fate decisions and differentiation, including TP63, SOX2, ECT2, and PIK3CA. Furthermore, novel targetable oncogenic kinases within this amplicon include PRKCI, PAK2, MAP3K13, and TNIK. TCGA analysis of these genes identified amplification in more than 20% of clinical squamous cell carcinoma samples, correlating with a significant decrease in overall patient survival. Alteration of these genes frequently co-occurs and is dependent on 3q-chromosome amplification. The dependency of cancer cells on these amplified kinases provides a route toward personalized medicine in squamous cell carcinoma patients through development of small-molecules targeting these kinases.

scholarly journals Whole exome sequencing and deep sequencing of esophageal squamous cell carcinoma and adenocarcinoma in Japanese patients using the Japanese version of the Genome Atlas, JCGA

Esophagus ◽  
2021 ◽  
Author(s):  
Eisuke Booka ◽  
Yasuhiro Tsubosa ◽  
Tomoya Yokota ◽  
Shuhei Mayanagi ◽  
Kenjiro Ishii ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Somatic Mutations ◽  
Molecular Targets ◽  
Japanese Version ◽  
Japanese Patients ◽  
Genetic Alterations ◽  
Genome Atlas

Abstract Background Recent comprehensive mutation analyses have revealed a relatively small number of driver mutations in esophageal cancer, implicating a limited number of molecular targets, most of which are also implicated in squamous cell carcinoma. Methods In this study, we investigated genetic alterations in 44 esophageal squamous cell carcinomas (ESCC) and 8 adenocarcinomas (EAC) from Japanese patients as potential molecular targets, based on data from the Japanese version of The Genome Atlas (JCGA). Results Esophageal cancer was characterized by TP53 somatic mutations in ESCC (39/44, 88.6%) and EAC (5/8, 62.5%). In addition to TP53 mutations, somatic mutations in NFE2L2 (16/44, 36.4%), CDKN2A (7/44, 15.9%), and KMT2D (7/44, 15.9%) were more frequently detected in ESCC than in EAC. WRN-truncated type mutations that lead to genomic instability correlate with EAC, but not ESCC. ESCC samples were enriched in ALDH2-associated mutational signature 16 as well as the APOBEC signature. Patients with FAT2 mutations had significantly poorer overall survival compared with those with wild-type status at FAT2 (p < 0.05). Patients with EP300 or PTPRD mutations also had poor progression-free survival compared with respective wild-types (p < 0.05 or p < 0.001). Conclusions These findings may facilitate future precision medicine approaches based on genomic profiling in ESCC and EAC.

scholarly journals Anal squamous cell carcinoma in a high HIV prevalence population

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Danielle R. L. Brogden ◽  
Christopher C. Khoo ◽  
Christos Kontovounisios ◽  
Gianluca Pellino ◽  
Irene Chong ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Disease Free Survival ◽  
Hiv Positive ◽  
Anal Squamous Cell Carcinoma ◽  
Free Survival ◽  
Persons Living With Hiv ◽  
Disease Free ◽  
Hiv Negative

AbstractAnal Squamous Cell Carcinoma (ASCC) is a rare cancer that has a rapidly increasing incidence in areas with highly developed economies. ASCC is strongly associated with HIV and there appears to be increasing numbers of younger male persons living with HIV (PLWH) diagnosed with ASCC. This is a retrospective cohort study of HIV positive and HIV negative patients diagnosed with primary ASCC between January 2000 and January 2020 in a demographic group with high prevalence rates of HIV. One Hundred and seventy six patients were included, and clinical data was retrieved from multiple, prospective databases. A clinical subgroup was identified in this cohort of younger HIV positive males who were more likely to have had a prior diagnosis of Anal Intraepithelial Neoplasia (AIN). Gender and HIV status had no effect on staging or disease-free survival. PLWH were more likely to develop a recurrence (p < 0.000) but had a longer time to recurrence than HIV negative patients, however this was not statistically significant (46.1 months vs. 17.5 months; p = 0.077). Patients known to have a previous diagnosis of AIN were more likely to have earlier staging and local tumour excision. Five-year Disease-Free Survival was associated with tumour size and the absence of nodal or metastatic disease (p < 0.000).

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