Concordant analysis of KRAS, BRAF, PIK3CA mutations and PTEN expression between primary colorectal cancer and matched metastases

Chen, Mao; Wu, Xinyin; Yang, Zu‐Yao; Threapleton, Diane; Yuan, Jinqiu; Yu, Yuanyuan; Tang, Jinliang

doi:10.1038/srep08065

Cited by 94 publications

(98 citation statements)

References 51 publications

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“…In malignancies where targeted therapies have been more successful, including lung cancer and melanoma, analysis of paired primary and metastatic biopsies revealed 90% to 100% concordance of EGFR or BRAF mutations (12)(13)(14). Comparative analyses of matched primary/metastatic colorectal tumors revealed >90% concordance of KRAS, BRAF, and PIK3CA mutations (15)(16)(17). In breast cancer, ERBB2 testing has been shown to be concordant between primary tumors and metastases in >90% of cases (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma

et al. 2018

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Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited effi cacy. A potential reason for the failure of such therapies is that genomic profi ling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, fi nding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed signifi cant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplifi cation profi les commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifi cations not detected in PT sampling. Lastly, we profi led paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profi ling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profi ling to enhance selection of therapy. SIGNIFICANCE:We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profi ling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1);[37][38][39][40][41][42][43][44][45][46][47][48]

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Section: Introductionmentioning

confidence: 99%

Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma

et al. 2018

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“…Laboratories must either validate their own independent test or adopt a commercially available kit. Concordance between primary tumors and metastatic lesions is high, ranging between 90% and 100% in most studies, suggesting that testing can be completed on whichever lesion is easiest to biopsy, or on archival tissue (17)(18)(19)(20)(21)(22). While highly conserved between liver metastasis and primary, some studies have suggested a higher level of discordance (up to 32%) between primary and lung or lymph node metastasis, which may complicate mutation analysis in patients with metastases beyond the liver (23,24).…”

Section: Overview and Clinical Significancementioning

confidence: 99%

“…(v-raf murine sarcoma viral oncogene B1) status with high concordance to primary lesions (17,19,(25)(26)(27). While conventional assays identify patients as RAS mutant when a mutation is detected in >10% of reads sequenced, sensitivities approaching 0.1% are now possible (28).…”

Section: Pik3camentioning

confidence: 99%

Current companion diagnostics in advanced colorectal cancer; getting a bigger and better piece of the pie

Loree

Kopetz

Raghav

2017

J. Gastrointest. Oncol.

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While the treatment of colorectal cancer continues to rely heavily on conventional cytotoxic therapy, an increasing number of targeted agents are under development. Many of these treatments require companion diagnostic tests in order to define an appropriate population that will derive benefit. In addition, a growing number of biomarkers provide prognostic information about a patient's malignancy. As we learn more about these biomarkers and their assays, selecting the appropriate companion diagnostic becomes increasingly important. In the case of many biomarkers, there are numerous assays which could provide the same information to a treating physician, however each assay has strengths and weaknesses. Institutions must balance cost, assay sensitivity, turn-around time, and labor resources when selecting which assay to offer. In this review we will discuss the current state of companion diagnostics available in metastatic colorectal cancer and explore emerging biomarkers and their assays. We will focus on KRAS, BRAF, HER2, and PIK3CA testing, as well as microsatellite stability assessment and multigene panels.

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“…27,28 Many biologicals are being developed targeting the same molecular mechanism, yet the expressions may change over time making the drug less or more effective. 29 For clinical trial design, such dynamic behavior is hard to control for and potentially may lead to misclassification affecting the power of the study.…”

Section: Consequences For Trial Design and Analysis In Pmmentioning

confidence: 99%

Implementation of comparative effectiveness research in personalized medicine applications in oncology: current and future perspectives

IJzerman¹,

Manca

Keizer

et al. 2015

CER

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Personalized medicine (PM) or precision medicine has been defined as an innovative approach that takes into account individual differences in people's genes, environments, and lifestyles in prevention and treatment of disease. In PM, genomic information may contribute to the molecular understanding of disease, to optimize preventive health care strategies, and to fit the best drug therapies to the patient's individual characteristics. Evidence development in the era of genomic medicine is extremely challenging due to a number of factors. These include the rapid technological innovation in molecular diagnostics and targeted drug discoveries, and hence the large number of mutations and multiple ways these may influence treatment decisions. Although the evidence base for PM is evolving rapidly, the main question to be explored in this article is whether existing evidence is also fit for comparative effectiveness research (CER). As a starting point, this paper therefore reflects on the evidence required for CER and the evidence gaps preventing decisions on market access and coverage. The paper then discusses challenges and potential barriers for applying a CER paradigm to PM, identifies common methodologies for designing clinical trials in PM, discusses various approaches for analyzing clinical trials to infer from population to individual level, and presents an example of a clinical trial in PM (The RxPONDER TRIAL) demonstrating good practice. The paper concludes with a future perspective, including modeling approaches for evidence synthesis.

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Concordant analysis of KRAS, BRAF, PIK3CA mutations and PTEN expression between primary colorectal cancer and matched metastases

Cited by 94 publications

References 51 publications

Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma

Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma

Current companion diagnostics in advanced colorectal cancer; getting a bigger and better piece of the pie

Implementation of comparative effectiveness research in personalized medicine applications in oncology: current and future perspectives

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