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  • American Society of Clinical Oncology (ASCO)  (2)
  • 1
    In: Journal of Global Oncology, American Society of Clinical Oncology (ASCO), Vol. 5, No. suppl ( 2019-10-07), p. 55-55
    Abstract: 55 Background: The identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with non-small-cell lung cancer (NSCLC). Although tumor tissue biopsy remains the gold standard for diagnosis of NSCLC, the analysis of plasma circulating tumor DNA (ctDNA), known as liquid biopsy, has recently emerged as an alternative and noninvasive approach for exploring tumor genetic constitution. In this study, we developed a mutation detection approach for liquid biopsy using ultra-deep massively parallel sequencing (MPS) with unique molecular identifier (UID) tagging and evaluated its performance for the identification and quantification of tumor-derived mutations from plasma of patients with advanced NSCLC. Methods: Tissue biopsy and plasma samples were collected from a total of 58 patients diagnosed with NSCLC in Vietnam. Genetic alterations in four driver genes including EGFR, KRAS, NRAS and BRAF were identified by using ultra-deep MPS combined with UID tagging. Subsequently, the concordance rate of mutation testing between matched plasma and tissue samples was assessed. Additionally, a commercially available ddPCR (Bio-rad) assay was used to conduct a cross-platform comparison with ultra-deep MPS for the detection and quantification of the three most common actionable EGFR mutations (del19, L858R and T790M). Results: Compared to the mutations detected in paired tissue samples, the plasma based ultra-deep MPS achieved high concordance rate of 87.5%. Cross-platform comparison with droplet digital PCR demonstrated comparable detection performance (91.4% concordance, Cohen's kappa coefficient of 0.85 with 95% CI = 0.72 – 0.97) and great reliability in quantification of mutation allele frequency (Intraclass correlation coefficient of 0.96 with 95% CI = 0.90 – 0.98). Conclusions: Our results highlight the potential application of liquid biopsy using ultra-deep MPS as a routine assay in clinical practice for both detection and quantification of actionable mutation landscape in NSCLC patients.
    Type of Medium: Online Resource
    ISSN: 2378-9506
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 3018917-2
    detail.hit.zdb_id: 2840981-4
    Location Call Number Limitation Availability
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  • 2
    In: Journal of Global Oncology, American Society of Clinical Oncology (ASCO), Vol. 5, No. suppl ( 2019-10-07), p. 54-54
    Abstract: 54 Background: Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer and leading cause of cancer related death worldwide. Acquired genetic alterations in major driver genes including EGFR, KRAS, NRAS, BRAF, ALK and ROS1 are the most common mutations in NSCLC and certain mutations are associated with drug sensitivity or resistance. Hence, the mutation profiles of NSCLC patients are vital to guide targeted therapy and monitor the tumor recurrence, thereby improving the survival rate. The latest Globocan data showed that lung cancer ranks as the second most common cancer in Vietnam with high incidence and mortality rate. Nonetheless, the mutation spectrum of Vietnamese NSCLC patients has not been profiled thoroughly and current views on mutation testing largely rely on data obtained from previous prospective studies in Caucasian or East Asian cohorts. Methods: Massive parallel sequencing was employed to detect both somatic point mutations and rearrangement in six major driver genes in tissue biopsies from 350 NSCLC patients in Vietnam. The χ2/Fisher’s exact test was performed to compare mutation frequency between different cohorts. Additionally, both univariate and multivariate tests were used to identify clinical factors associated with mutation prevalence. Results: EGFR (32.3%) and KRAS (20%) accounted for the most frequently mutated genes, followed by ALK (5.4%), ROS1 (2.9%), BRAF (1.1%) and NRAS (0.6%). Our data showed a unique pattern of mutation profiles in Vietnamese NSCLC patients, with significant enrichment of KRAS mutation as compared to reported East Asian cohorts (20% versus 8%-10%, p 〈 0.05). Furthermore, EGFR and KRAS mutation frequencies were significantly associated with patients’ gender, with EGFR mutations more commonly detected in female than in male (48.1% versus 26.9%, p 〈 0.00001) while higher KRAS mutation frequency in male than in female (30.7% versus 9.2%, p 〈 0.0001). Young patients aged below the median age of 61 years had significantly higher tendency to acquire rearrangements in ALK (p = 0.02) and ROS1 (p = 0.03) than elderly patients. Conclusions: To our knowledge, our study is the first to reveal the mutation profiles of major druggable genes in a large cohort of Vietnamese NSCLC patients.
    Type of Medium: Online Resource
    ISSN: 2378-9506
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 3018917-2
    detail.hit.zdb_id: 2840981-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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