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

Abstract

Squamous 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.

Utility ofCYP2D6copy number variants as prognostic biomarker in localized anal squamous cell carcinoma

“…These four patients were excluded for the survival analyses. This cohort has been described in previous works 12,13,27 . A summary of the clinical characteristics of this cohort is shown in Table 1.…”

Client Applications and Server-Side Docker for Management of RNASeq and/or VariantSeq Workflows and Pipelines of the GPRO Suite

“…"RNASeq" has been successfully tested in several transcriptomics studies using distinct reference sequences and experimental backgrounds [56,[58][59][60]. "VariantSeq" has also been validated across distinct studies for variant analysis and different experimental contexts [57,61,62]. In addition, two tutorials (one for each application) have also been created, and are here included, to provide users with training material to familiarize themselves with each application (links for the tutorials are provided in the section below, Data Availability Statement).…”