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Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal
Paula Sánchez-Fernández1, Cristina Riobello2, María Costales1
1Department Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain.
Abstract:
Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.
Insights
Identifying actionable gene mutations in intestinal-type sinonasal adenocarcinoma (ITAC) offers new personalized therapy options. Thorough germline DNA analysis is crucial for accurate somatic mutation interpretation in ITAC patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare cancer with a poor prognosis.
- There is a critical need for novel, targeted treatment strategies for ITAC.
- Understanding the molecular landscape of ITAC is essential for developing personalized therapies.
Purpose of the Study:
- To identify actionable gene mutations in ITAC.
- To guide the development of personalized, target-specific therapies for ITAC patients.
- To investigate the role of germline DNA in somatic mutation analysis.
Main Methods:
- Next-generation sequencing (NGS) of a 120-gene panel was performed on 48 tumor and 27 matched germline DNA samples.
- Comprehensive analysis of sequence variants, distinguishing between germline and somatic mutations.
- Identification of frequently mutated genes and affected signaling pathways.
Main Results:
- 58 somatic variants in 33 genes were identified in 20 out of 27 cases.
- PIK3CA, APC, ATM, KRAS, NF1, LRP1B, and BRCA1 were among the most frequently mutated genes.
- Somatic mutations affected PI3K, MAPK/ERK, WNT, and DNA repair pathways.
- Potentially actionable mutations, including biomarkers for FDA-approved therapies, were found in 8 cases.
Conclusions:
- Accurate interpretation of somatic mutations in ITAC necessitates concurrent germline DNA sequencing.
- The study identified potentially actionable mutations, paving the way for personalized treatment strategies.
- These findings open new avenues for targeted therapeutic interventions in ITAC.
