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Assessing the clinical value of targeted massively parallel sequencing in a longitudinal, prospective population-based study of cancer patients.

Wong SQ, Fellowes A, Doig K, Ellul J, Bosma TJ, Irwin D, Vedururu R, Tan AY, Weiss J, Chan KS, Lucas M, Thomas DM, Dobrovic A, Parisot JP, Fox SB - Br. J. Cancer (2015)

Bottom Line: A subset of patients was validated for canonical mutations using the Agena Bioscience MassARRAY system with 100% concordance.Whereas the prevalence of mutations was consistent with other institutionally based series for some tumour streams (breast carcinoma and colorectal adenocarcinoma), others were different (lung adenocarcinoma and head and neck squamous cell carcinoma), which has significant implications for health economic modelling of particular targeted agents.Actionable mutations in tumours not usually thought to harbour such genetic changes were also identified.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia [2] Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia.

ABSTRACT

Introduction: Recent discoveries in cancer research have revealed a plethora of clinically actionable mutations that provide therapeutic, prognostic and predictive benefit to patients. The feasibility of screening mutations as part of the routine clinical care of patients remains relatively unexplored as the demonstration of massively parallel sequencing (MPS) of tumours in the general population is required to assess its value towards the health-care system.

Methods: Cancer 2015 study is a large-scale, prospective, multisite cohort of newly diagnosed cancer patients from Victoria, Australia with 1094 patients recruited. MPS was performed using the Illumina TruSeq Amplicon Cancer Panel.

Results: Overall, 854 patients were successfully sequenced for 48 common cancer genes. Accurate determination of clinically relevant mutations was possible including in less characterised cancer types; however, technical limitations including formalin-induced sequencing artefacts were uncovered. Applying strict filtering criteria, clinically relevant mutations were identified in 63% of patients, with 26% of patients displaying a mutation with therapeutic implications. A subset of patients was validated for canonical mutations using the Agena Bioscience MassARRAY system with 100% concordance. Whereas the prevalence of mutations was consistent with other institutionally based series for some tumour streams (breast carcinoma and colorectal adenocarcinoma), others were different (lung adenocarcinoma and head and neck squamous cell carcinoma), which has significant implications for health economic modelling of particular targeted agents. Actionable mutations in tumours not usually thought to harbour such genetic changes were also identified.

Conclusions: Reliable delivery of a diagnostic assay able to screen for a range of actionable mutations in this cohort was achieved, opening unexpected avenues for investigation and treatment of cancer patients.

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Related in: MedlinePlus

The prevalence of mutations in common cancer genes from the Cancer 2015 cohorts compared with other institutional-based series. Reported prevalence of mutations in colorectal adenocarinoma, breast-invasive carcinoma, lung adenocarcinoma and head and neck squamous cell carcinoma as reported by public mutational catalogues (COSMIC and TCGA) compared with the Cancer 2015 cohort.
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fig3: The prevalence of mutations in common cancer genes from the Cancer 2015 cohorts compared with other institutional-based series. Reported prevalence of mutations in colorectal adenocarinoma, breast-invasive carcinoma, lung adenocarcinoma and head and neck squamous cell carcinoma as reported by public mutational catalogues (COSMIC and TCGA) compared with the Cancer 2015 cohort.

Mentions: To determine an accurate representation of mutations in the general population of cancer patients, we compared the prevalence of mutations with the COSMIC and TCGA databases to those observed in this study (Figure 3). Examination of both colorectal adenocarcinoma and breast-invasive carcinoma cases found no significant difference in the prevalence of mutations for both tumour types across all data sets. There was, however, some noticeable differences in the invasive breast carcinoma group including the lack of AKT1 mutations reported in the TCGA data set and the higher rate of ATM mutation in the Cancer 2015 data set.


Assessing the clinical value of targeted massively parallel sequencing in a longitudinal, prospective population-based study of cancer patients.

Wong SQ, Fellowes A, Doig K, Ellul J, Bosma TJ, Irwin D, Vedururu R, Tan AY, Weiss J, Chan KS, Lucas M, Thomas DM, Dobrovic A, Parisot JP, Fox SB - Br. J. Cancer (2015)

The prevalence of mutations in common cancer genes from the Cancer 2015 cohorts compared with other institutional-based series. Reported prevalence of mutations in colorectal adenocarinoma, breast-invasive carcinoma, lung adenocarcinoma and head and neck squamous cell carcinoma as reported by public mutational catalogues (COSMIC and TCGA) compared with the Cancer 2015 cohort.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4402458&req=5

fig3: The prevalence of mutations in common cancer genes from the Cancer 2015 cohorts compared with other institutional-based series. Reported prevalence of mutations in colorectal adenocarinoma, breast-invasive carcinoma, lung adenocarcinoma and head and neck squamous cell carcinoma as reported by public mutational catalogues (COSMIC and TCGA) compared with the Cancer 2015 cohort.
Mentions: To determine an accurate representation of mutations in the general population of cancer patients, we compared the prevalence of mutations with the COSMIC and TCGA databases to those observed in this study (Figure 3). Examination of both colorectal adenocarcinoma and breast-invasive carcinoma cases found no significant difference in the prevalence of mutations for both tumour types across all data sets. There was, however, some noticeable differences in the invasive breast carcinoma group including the lack of AKT1 mutations reported in the TCGA data set and the higher rate of ATM mutation in the Cancer 2015 data set.

Bottom Line: A subset of patients was validated for canonical mutations using the Agena Bioscience MassARRAY system with 100% concordance.Whereas the prevalence of mutations was consistent with other institutionally based series for some tumour streams (breast carcinoma and colorectal adenocarcinoma), others were different (lung adenocarcinoma and head and neck squamous cell carcinoma), which has significant implications for health economic modelling of particular targeted agents.Actionable mutations in tumours not usually thought to harbour such genetic changes were also identified.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia [2] Division of Cancer Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia.

ABSTRACT

Introduction: Recent discoveries in cancer research have revealed a plethora of clinically actionable mutations that provide therapeutic, prognostic and predictive benefit to patients. The feasibility of screening mutations as part of the routine clinical care of patients remains relatively unexplored as the demonstration of massively parallel sequencing (MPS) of tumours in the general population is required to assess its value towards the health-care system.

Methods: Cancer 2015 study is a large-scale, prospective, multisite cohort of newly diagnosed cancer patients from Victoria, Australia with 1094 patients recruited. MPS was performed using the Illumina TruSeq Amplicon Cancer Panel.

Results: Overall, 854 patients were successfully sequenced for 48 common cancer genes. Accurate determination of clinically relevant mutations was possible including in less characterised cancer types; however, technical limitations including formalin-induced sequencing artefacts were uncovered. Applying strict filtering criteria, clinically relevant mutations were identified in 63% of patients, with 26% of patients displaying a mutation with therapeutic implications. A subset of patients was validated for canonical mutations using the Agena Bioscience MassARRAY system with 100% concordance. Whereas the prevalence of mutations was consistent with other institutionally based series for some tumour streams (breast carcinoma and colorectal adenocarcinoma), others were different (lung adenocarcinoma and head and neck squamous cell carcinoma), which has significant implications for health economic modelling of particular targeted agents. Actionable mutations in tumours not usually thought to harbour such genetic changes were also identified.

Conclusions: Reliable delivery of a diagnostic assay able to screen for a range of actionable mutations in this cohort was achieved, opening unexpected avenues for investigation and treatment of cancer patients.

Show MeSH
Related in: MedlinePlus