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Varsha Singh
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-22 - Liquid Biopsy in the Detection of EGFR Activating and Resistance Mutations in Advanced Pulmonary Adenocarcinoma (Now Available) (ID 1761)
08:00 - 18:00 | Presenting Author(s): Varsha Singh
- Abstract
Background
Approximately 30% of the advanced pulmonary adenocarcinoma (PADC) patients are found to be mutated with epidermal growth factor receptor (EGFR). Nearly 60% of EGFR mutated patients develop T790M resistance mutation against which third generation TKIs are available. Detection of T790M mutation is a challenge due to non availability of enough tumour tissues in patients receiving first-generation EGFR-TKI treatment. Liquid biopsies (cell- free DNA) are promising for detection of EGFR activating and resistance mutations. The current study focuses on detection of EGFR mutations in cell-free DNA from patients with histologically confirmed EGFR mutation status.
Method
50 PADC patients (22 males; 28 females with mean age 63 years) were studied for EGFR mutations. Out of them 40 were TKI naïve and 10 patients were treated with EGFR-TKIs. Follow up biopsy from TKI treated patients was not available for resistant mutation studies. Real-time PCR and Digital droplet PCR techniques were adopted for studying EGFR exon 19 (deletions), 20 (T790M) and 21 (L858R) mutations in tissue and plasma samples respectively.
Result
Clinically all patients were in stage III-IV and 52% were never smokers. Out of 40 TKI naive cases, 20 cases were positive for EGFR activating mutations in tissue and 17 in plasma. Twenty cases were negative for EGFR mutations in both tissue and plasma. In 10 EGFR-TKI treated patients, founder activating mutation was still present in plasma of 7 cases and 3 of them also showed T790M resistance mutation. Two patients carrying this resistant mutation died subsequently. Remaining three TKI treated patients did not harbour even founder activating mutation in the plasma.
Conclusion
We observed a concordance of 88% (44/50) between liquid biopsy and tumour tissue. Our study highlights role of liquid biopsy as an alternative for detecting EGFR activating and resistance mutations in advanced PADC. EGFR mutation analysis in liquid biopsy can be helpful in those patients where the tissue biopsy is not possible.
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-48 - Whole Exome Sequencing (WES) in Non-Small Cell Lung Carcinoma (NSCLC): Identification of Novel Biomarkers (Now Available) (ID 1712)
09:45 - 18:00 | Presenting Author(s): Varsha Singh
- Abstract
Background
Significant advancement has been made in the treatment of patients with pulmonary adenocarcinoma (ADC) on the basis of the molecular profile. However, no such molecular target exists for squamous cell carcinoma (SCC) or small cell lung cancer (SCLC). WES has been in wide use for the discovery of new genetic markers, which may offer more information for the development of personalized medicine for all subtypes of lung cancer. The aim of the current study is to find out novel genetic markers for NSCLC which can be used as a universal biomarker for the treatment.
Method
WES of 20 advanced NSCLC patients (10 ADC and 10 SCC) was done on the Illumina HiSeqX10 with paired end 151bp chemistry. The Male: female ratio was 5.6:1 and a median age 56 years. Only 3 patients were non-smoker and in one case smoking history was unknown. 75% of patients were present with co-morbidities, all patients were either in stage III or IV and performance status was either 1 or 2.
Result
Table 1: WES data statistics and the total number of variants identified: S.No WES data Numbers 1 Average raw data 13.6 GB 2 Average processed data 12.1 GB 3 Average reads aligned 80.2% 4 Average total variations 34173 5 Average SNPs 26030 6 Average INDEL 81423 7 Average frameshift deletions 2185 8 Average frameshift insertions 3571 9 Average non-frameshift deletions 368 10 Average non-frameshift insertions 1292 11 Average non-synonymous 13418 12 Average stop gain 10337 13 Average stop loss 38 14 Average synonymous SNPs 11607 15 Average variations reported in databases 20269 16 Unknown mutations 659 WES data statistics has been depicted in table 1 including number of variants identified. After excluding common variants (MAF > 0.05), a total of 23 rare variants (0 < MAF < 0.01), possibly linked to lung carcinoma was identified in the exome. Further stringent filtering showed allele frequencies of mutations in GPRIN2 (G protein-regulated inducer of neurite outgrowth 2), KCNJ18 (potassium voltage-gated channel subfamily J member 18) and TEKT4 (Tektin 4) genes which were present in all the cases. The variations of amino acid substitutions were i) TEKT4: p.A223T and p.A405T (rs75603622); ii) GPRIN2: p.V241M (rs9422022), p.V47M (rs3127819); iii) KCNJ18: p.L211F (rs1435776313), p.I262S (rs1450551937)
Conclusion
Although the mechanism of GPRIN2, KCNJ12 and TEKT4 in tumorigenesis is unclear; our results suggest that these may play a major role in NSCLC and it is worth to be investigated in future. Validation of these genes is under process.
