Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients
2
조회
0
다운로드
4
인용
0
참고문헌
키워드
초록
Purpose With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. Materials and Methods To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. Results We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. Conclusion In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Abstract
Purpose With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. Materials and Methods To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. Results We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. Conclusion In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
참고문헌 (31)
- Meyerson M, "Advances in understanding cancer genomes through second-generation sequencing", Nat Rev Genet, 11, pp.685~696 (2010)
- Zehir A, "Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10, 000 patients", Nat Med, 23, pp.703~713 (2017)
- Katsnelson A, "Momentum grows to make 'personalized' medicine more 'precise'", Nat Med, 19, pp.249~ (2013)
- Cancer Genome Atlas Research Network, "Comprehensive molecular profiling of lung adenocarcinoma", Nature, 511, pp.543~550 (2014)
- Frampton GM, "Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing", Nat Biotechnol, 31, pp.1023~1031 (2013)
- Cho YS, "An ethnically relevant consensus Korean reference genome is a step towards personal reference genomes", Nat Commun, 7, pp.13637~ (2016)
- Schadt EE, "Computational solutions to large-scale data management and analysis", Nat Rev Genet, 11, pp.647~657 (2010)
- Hynes SO, "Tissue-based next generation sequencing : application in a universal healthcare system", Br J Cancer, 116, pp.553~560 (2017)
- Shin HT, "Prevalence and detection of low-allele-fraction variants in clinical cancer samples", Nat Commun, 8, pp.1377~ (2017)
- Lee S, "Korean Variant Archive(KOVA) : a reference database of genetic variations in the Korean population", Sci Rep, 7, pp.4287~ (2017)
- Guyard A, "DNA degrades during storage in formalin-fixed and paraffin-embedded tissue blocks", Virchows Arch, 471, pp.491~500 (2017)
- Cancer Genome Atlas Research Network, "Comprehensive genomic characterization of squamous cell lung cancers", Nature, 489, pp.519~525 (2012)
- George J, "Comprehensive genomic profiles of small cell lung cancer", Nature, 524, pp.47~53 (2015)
- Peifer M, "Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer", Nat Genet, 44, pp.1104~1110 (2012)
- Cancer Genome Atlas Research Network, "Comprehensive molecular characterization of gastric adenocarcinoma", Nature, 513, pp.202~209 (2014)
- Cancer Genome Atlas Network, "Comprehensive molecular characterization of human colon and rectal cancer", Nature, 487, pp.330~337 (2012)
- 임선민, "Rare Incidence of ROS1 Rearrangement in Cholangiocarcinoma", Cancer Research and Treatment, 49(1), pp.185~192 (2017), 대한암학회
- Menis J, "New clinical research strategies in thoracic oncology : clinical trial design, adaptive, basket and umbrella trials, new end-points and new evaluations of response", Eur Respir Rev, 23, pp.367~378 (2014)
- Jordan EJ, "Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies", Cancer Discov, 7, pp.596~609 (2017)
- Rizvi NA, "Cancer immunology : mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer", Science, 348, pp.124~128 (2015)
- Lee B, "Clinicopathologic characteristics of EGFR, KRAS, and ALK alterations in 6,595 lung cancers", Oncotarget, 7, pp.23874~23884 (2016)
- Alexandrov LB, "Signatures of mutational processes in human cancer", Nature, 500, pp.415~421 (2013)
- Kandoth C, "Mutational landscape and significance across 12 major cancer types", Nature, 502, pp.333~339 (2013)
- Souilmi Y, "Scalable and cost-effective NGS genotyping in the cloud", BMC Med Genomics, 8, pp.64~ (2015)
- Pfundt R, "Detection of clinically relevant copy-number variants by exome sequencing in a large cohort of genetic disorders", Genet Med, 19, pp.667~675 (2017)
- Cho M, "Tissue recommendations for precision cancer therapy using next generation sequencing : a comprehensive single cancer center's experiences", Oncotarget, 8, pp.42478~42486 (2017)
- Austin MC, "DNA yield from tissue samples in surgical pathology and minimum tissue requirements for molecular testing", Arch Pathol Lab Med, 140, pp.130~133 (2016)
- Lee C, "A method to evaluate the quality of clinical gene-panel sequencing data for single-nucleotide variant detection", J Mol Diagn, 19, pp.651~658 (2017)
- Hagemann IS, "Clinical next-generation sequencing in patients with non-small cell lung cancer", Cancer, 121, pp.631~639 (2015)
- Alix-Panabieres C, "Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy", Cancer Discov, 6, pp.479~491 (2016)
- Kim ST, "Prospective blinded study of somatic mutation detection in cell-free DNA utilizing a targeted 54-gene next generation sequencing panel in metastatic solid tumor patients", Oncotarget, 6, pp.40360~40369 (2015)