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. 2023 Oct 5;18(10):e0292087.
doi: 10.1371/journal.pone.0292087. eCollection 2023.

Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population

Udit Nindra  1   2   3   4   5 , Abhijit Pal  1   3   4 , Vivienne Lea  6 , Stephanie Hui-Su Lim  2   4   5 , Kate Wilkinson  1 , Ray Asghari  3 , Tara L Roberts  4   5   7 , Therese M Becker  4   5   7 , Mahtab Farzin  6 , Tristan Rutland  5   6 , Mark Lee  7 , Scott MacKenzie  5 , Weng Ng  1   4   5   7 , Bin Wang  6 , C Soon Lee  3   5   6   7 , Wei Chua  1   4   5   7
Affiliations

Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population

Udit Nindra et al. PLoS One. .

Abstract

Background: Next generation sequencing (NGS) is increasingly used in standard clinical practice to identify patients with potentially actionable mutations. Stratification of NGS mutation tiers is currently based on the European Society of Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT[E]) Tier I-V & X. Allele frequency is also increasingly recognised as an important prognostic tool in advanced cancer. The aim of this study was to determine the genomic mutations in metastatic colorectal cancer (CRC) in an Australian multicultural population and their influence on survival outcomes.

Methods: Next generation sequencing with the 50-gene panel Oncomine Precision Assay™ was used on 180 CRC tissue samples obtained across six Sydney hospitals between June 2021 and March 2022.

Results: From 180 samples, 147 (82%) had at least one gene mutation identified with 68 (38%) having two or more concurrent mutations. Tier I variants included RAS wild-type [EI] in 73 (41%) and BRAF V600E [EIA] in 27 (15%). Non-tier I variants include 2 (1%) ERBB2 amplification [EIIB], 26 (15%) PIK3CA hotspot mutations [EIIIA] and 9 (5%) MET focal amplifications [EIIIA]. NGS testing revealed an additional 22% of cases with Tier II & III mutations. 43% of patients also presented with potentially actionable Tier III & IV mutations. Patients with concurrent TP53 and RAS mutations had significantly reduced overall survival (6.1 months versus 21.1 months, p <0.01). High KRAS allele frequency, as defined by those with over 20% variant allele frequency (VAF), also demonstrated reduced overall survival (12.1 months versus 42.9 months, p = 0.04).

Conclusions: In addition to identifying patients with genomic alterations suitable for clinically proven standard of care therapeutic options, the 50 gene NGS panel has significant potential in identifying potentially actionable non-tier 1 mutations and therefore may become future standard clinical practice.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Distribution of concurrent mutations identified by next generation sequencing in colorectal cancer.
Individual patients with concurrent mutations in each column. Tiers 1–3 as outlined by the European Society of Medical Oncology Scale for Clinical Actionability of Molecular Targets.
Fig 2
Fig 2. Overall survival of RAS-mutated metastatic colorectal cancer with and without concurrent P53 mutations.
Kaplan-Meier curve comparing TP53 wildtype (yellow) vs TP53 mutated (blue) patient outcomes. Dotted line represents median (6.1 months versus 21.1 months, HR 4.2, 95% CI 1.7–10.6, p <0.01).
Fig 3
Fig 3. Overall survival of RAS-mutated metastatic colorectal cancer based on allele frequency.
Kaplan-Meier curve comparing KRAS high variant allele frequent as defined by over 20% (yellow) vs KRAS low variant allele frequent as defined by below 20% (blue). Dotted line represents median (12.1 months versus not reached, HR 2.2, 95%CI 1.3–6.7, p = 0.04).
See this image and copyright information in PMC

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