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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Potentially actionable molecular alterations in particular related to poor oncologic outcomes in salivary gland
Julia Pikul1, Marcin M Machnicki2, Anna Rzepakowska3
1Department of Otorhinolaryngology, Head and Neck Surgery, Medical University of Warsaw, Warsaw, Poland.
Aim:
The study was designed to evaluate molecular alterations, relevant to the prognosis and personalized therapy of salivary gland cancers (SGCs).
Materials And Methods:
DNA was extracted from archival tissue of 40 patients with various SGCs subtypes. A targeted next-generation sequencing (NGS) panel was used for the identification of small-scale mutations, focal and chromosomal arm-level copy number changes. The final analysis included selected genes with potential actionable aberrations for targeted therapies and outcome predictions in 37 tumours' samples.
Results:
The follow-up of the SGCs study cohort revealed disease recurrence or metastasis in 19 patients and indicated poor individual outcomes. The mean disease-free survival (DFS) within the poor outcome group was 2.4 years, and the overall survival (OS) was 5.4 years. The DFS and OS of the remaining 18 patients with favourable outcomes were 8.3 years. The genes most frequently affected with aberrations were NF1 (n = 9, 24%) and TP53 (n = 8, 22%), with increased occurrence observed in the poor outcome group: NF1 (n = 6, 32%) and TP53 (n = 6, 32%). CDKN2A biallelic deletion was the most common copy number variation (n = 5), and was detected in 4 cases with identified disease relapse. TERT promoter mutation and amplification were found in myoepithelial carcinoma. A p.Ile35Thr mutation was discovered in CTNNB1 in two cases of adenoid cystic carcinoma. ERBB2 alterations were remarkable for SDC ex PA. Furthermore, TP53 mutation was established as a relevant negative prognostic factor for overall survival (p = 0,04). The analysis revealed potentially actionable genes in detected alterations in: MECA 100% (1/1), SDC 100% (7/7), AD 92% (11/12), Ca ex PA 82% (18/22), MECA 65% (20/31), AdCC 64% (9/14) and AcCC 0% (0/1).
Conclusions:
SGCs are a heterogeneous group of malignancies with distinct molecular landscape that characterized by poor prognosis and inadequate treatment options. Nonstandard strategies might be beneficial for patients who suffer from salivary gland cancers. Wider utilization of NGS analysis may increase the opportunity for patients with those rare cancers to receive more precise, personalized therapy.
Insights
Salivary gland cancers (SGCs) exhibit diverse molecular profiles linked to poor prognosis. Identifying actionable mutations via next-generation sequencing (NGS) can guide personalized therapies for these rare malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Salivary gland cancers (SGCs) are a heterogeneous group of rare malignancies.
- Current treatment options are often inadequate, highlighting the need for improved prognostic markers and targeted therapies.
Purpose of the Study:
- To evaluate molecular alterations in SGCs.
- To identify genetic changes relevant for prognosis and personalized treatment strategies.
Main Methods:
- DNA extraction from 40 archival SGC tissue samples.
- Targeted next-generation sequencing (NGS) panel for mutation and copy number variation analysis.
- Analysis focused on 37 tumors with selected actionable gene aberrations.
Main Results:
- NF1 (24%) and TP53 (22%) were the most frequently altered genes, with higher rates in poor-outcome cases.
- TP53 mutations were associated with significantly poorer overall survival (p=0.04).
- Actionable alterations were identified in most SGC subtypes, with high percentages in Adenoid Cystic Carcinoma (AdCC) and Adenocarcinoma (AD).
Conclusions:
- SGCs present a complex molecular landscape with poor prognosis and limited therapeutic avenues.
- Next-generation sequencing (NGS) analysis is crucial for uncovering actionable targets.
- Personalized therapeutic strategies informed by NGS may improve outcomes for SGC patients.
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