Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population.
<h4>Background</h4>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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0292087&type=printable |
| _version_ | 1797637534218452992 |
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| author | Udit Nindra Abhijit Pal Vivienne Lea Stephanie Hui-Su Lim Kate Wilkinson Ray Asghari Tara L Roberts Therese M Becker Mahtab Farzin Tristan Rutland Mark Lee Scott MacKenzie Weng Ng Bin Wang C Soon Lee Wei Chua |
| author_facet | Udit Nindra Abhijit Pal Vivienne Lea Stephanie Hui-Su Lim Kate Wilkinson Ray Asghari Tara L Roberts Therese M Becker Mahtab Farzin Tristan Rutland Mark Lee Scott MacKenzie Weng Ng Bin Wang C Soon Lee Wei Chua |
| author_sort | Udit Nindra |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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. |
| first_indexed | 2024-03-11T12:49:50Z |
| format | Article |
| id | doaj.art-96a4f02f3945468bab367622f96e9e7b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-11T12:49:50Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-96a4f02f3945468bab367622f96e9e7b2023-11-04T05:33:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-011810e029208710.1371/journal.pone.0292087Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population.Udit NindraAbhijit PalVivienne LeaStephanie Hui-Su LimKate WilkinsonRay AsghariTara L RobertsTherese M BeckerMahtab FarzinTristan RutlandMark LeeScott MacKenzieWeng NgBin WangC Soon LeeWei Chua<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0292087&type=printable |
| spellingShingle | Udit Nindra Abhijit Pal Vivienne Lea Stephanie Hui-Su Lim Kate Wilkinson Ray Asghari Tara L Roberts Therese M Becker Mahtab Farzin Tristan Rutland Mark Lee Scott MacKenzie Weng Ng Bin Wang C Soon Lee Wei Chua Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population. PLoS ONE |
| title | Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population. |
| title_full | Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population. |
| title_fullStr | Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population. |
| title_full_unstemmed | Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population. |
| title_short | Multigene panel next generation sequencing in metastatic colorectal cancer in an Australian population. |
| title_sort | multigene panel next generation sequencing in metastatic colorectal cancer in an australian population |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0292087&type=printable |
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