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ORAL 22 - Moving Beyond a Smoking Related-Cancer to the Young, Never-smokers and Inherited Disease (ID 117)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
ORAL22.03 - Inter-, and Intratumoural Genomic Heterogeneity of Primary Pulmonary Adenocarcinoma in Never Smokers (ID 3231)
10:45 - 12:15 | Author(s): M. Windsor
Lung cancer in never smokers may be enriched with oncogenic drivers. To explore patterns genomic changes among and within NS-LC, we performed multi-region whole genome sequencing (WGS) of primary pulmonary adenocarcinoma (LUAC).
An observational study was performed on 8 cases of never-smoking LUAC resected with curative intent. Post-diagnostic residual fresh tumor was procured with informed consent, with constitutional samples from normal lung or blood. Selection criteria included: histologically confirmed LUAC; never-smoker [< 100 cigarettes in a lifetime]; no prior malignancy, cytotoxic therapy or thoracic radiotherapy. Tissue samples were procured by an anatomical pathologist (Table 1). Quality criteria were >40% tumor cellularity and <20% necrosis as assessed visually by 2 anatomical pathologists (Table 1). DNA was extracted using Qiagen AllPrep DNA/RNA Mini Kit and Blood Maxi Kit. WGS was performed on paired end libraries using Illumina's HiSeq 2000 platform (Table 1). Single nucleotide variants (SNVs) called by MuTect, Varscan, Strelka and SomaticSniper were considered ‘high priority’ if their predicted functional significance was ‘moderate’ or ‘high’ according to SNPEff. Genotyping was performed using Illumina’s HumanOmni2.5-8 array for copy number calling using the Genome Alteration Print tool.
14 tumour samples and 8 constitutional samples were sequenced (table 1). Figure 1 Common CNVs and SNVs were observed among and within cases (figure 1). Figure 2 In case 1, 3 of 6 (50%) genes harboring high priority variants were altered in all 4 regions. Similarly, for cases 2 and 3, 8/10 (80%) and 4/8 (50%) genes were altered by high priority variants in all regions.
Patterns of SNVs and CNVs in LUAC demonstrate areas of common genomic changes and significant inter-, and intratumoral heterogeneity. These findings have significant implications for our understanding of lung cancer biology, also diagnostic testing of lung cancer and clinical trial design.
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