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MA05.05 Genomic Profiles of Lung Cancer Associated with Idiopathic Pulmonary Fibrosis
S366
Journal of Thoracic Oncology
samples and subjected to quantitative and qualitative assessment. Sequencing for EGFR, KRAS, BRAF mutations was performed in adenocarcinoma/non-small cell lung cancer not otherwise specified (NSCLC-NOS) cases. Results: Samples were obtained in 41 patients. Cytological diagnosis was adenocarcinoma/NSCLC-NOS in 25 (61.0%), squamous cell carcinoma in 10 (24.4%), small cell lung cancer in 5 (12.2%), and carcinoid in 1 (2.4%) case. DNA extraction yielded a mean of 4.03mg, well above the minimum required quantity for targeted sequencing of 10ng (Table 1). DNA quality measured by DNA Integrity Number could be calculated in 35 (85%) cases with a mean of 8.9, where >7 is acceptable for sequencing (Table 1). Sequencing results of adenocarcinoma/NSCLC-NOS cases show mutations in EGFR in 6, KRAS in 8, BRAF in 1 case. Wild type was demonstrated in 6 cases. Molecular analysis of the corresponding study samples is proceeding. Table 1. DNA quantity and quality Histological subtype
Cases, n (%)
Mean DNA Mean DNA quantity Integrity (mg) Number (DIN)
Adenocarcinoma/ 25 (61.0) 3.83 NSCLC-NOS Squamous cell carcinoma 10 (24.4) 2.65 Small cell lung carcinoma 5 (12.2) 5.28 Carcinoid 1 (2.4) 16.24 Overall 41 4.03
8.8 9.0 9.0 9.1 8.9
Conclusion: A single EBUS-TBNA yields DNA of quantity and quality sufficient for molecular analysis, and is expected to be adequate for lung cancer genotyping. Keywords: EBUS-TBNA, lung cancer, Molecular
MA05.05 Genomic Profiles of Lung Cancer Associated with Idiopathic Pulmonary Fibrosis
Vol. 12 No. 1S
standardized consensus. However, despite recent progress in the understanding of pathogenesis and the treatment of LC in general population based on the advances in molecular genomics, the pathogenesis or molecular profiles of IPF-LC has been largely unknown to date. Methods: We assessed genomic profiles of IPF-LC using targeted exome-sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling were performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted using CNVkit with focal events determined by GISTIC 2.0, and pathway analysis (KEGG) using DAVID. Results: Germline mutations in TERT (rs2736100,n¼33) and CDKN1A (rs2395655,n¼27) linked with IPF risk were detected in most samples. A total of 410 somatic mutations were identified with an average of 11.7 per tumor including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop, 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C/T transitions despite extensive smoking histories across most study subjects, suggesting more associations with APOBEC3B-related mutagenesis in the process of IPF-LC development, rather than smoking. TP53 (22/35,62.9%) and BRAF (6/35,17.1%) genes were found significantly mutated in IPF-LC. Recurrent focal amplifications in 3 chromosomal loci (3q26.33, 7q31.2, and 12q14.3), and 9p21.3 deletion were identified, and genes associated with JAK-STAT signaling pathway were significantly amplified in IPF-LC (P¼0.012). Conclusion: IPF-LC is genetically characterized by the presence of somatic mutations reflecting viral and immune-related mutagenic processes in the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Keywords: idiopathic pulmonary fibrosis, genomic profile, lung cancer
Ji An Hwang, Deokhoon Kim, Soo Hyun Bae, Sung-Min Chun, Joon Seon Song, Mi Young Kim, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Sojung Park, Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang Asan Medical Center, Seoul/Korea, Republic of
MA05.06 Diagnosis of Chronic Obstructive Pulmonary Disease in Lung Cancer - A Population Based Study
Background: Idiopathic pulmonary fibrosis (IPF) is associated with an increased risk of lung cancer (LC) independent of the effect of cigarette smoking. The prognosis of IPF-associated LC (IPF-LC) is known to be worse than the lone IPF or LC mainly due to the complications accompanying LC treatment with no established or
John Goffin,1 Grace Tang,2 Gregory Pond,2 Sophie Corriveau3 1Oncology, Juravinski Cancer Centre, Hamilton/ON/Canada, 2Oncology, Ontario Clinical Oncology Group, McMaster University, Hamilton/ON/ Canada, 3Medicine, St. Joseph’s Hospital, Hamilton/ON/ Canada
Journal of Thoracic Oncology
samples and subjected to quantitative and qualitative assessment. Sequencing for EGFR, KRAS, BRAF mutations was performed in adenocarcinoma/non-small cell lung cancer not otherwise specified (NSCLC-NOS) cases. Results: Samples were obtained in 41 patients. Cytological diagnosis was adenocarcinoma/NSCLC-NOS in 25 (61.0%), squamous cell carcinoma in 10 (24.4%), small cell lung cancer in 5 (12.2%), and carcinoid in 1 (2.4%) case. DNA extraction yielded a mean of 4.03mg, well above the minimum required quantity for targeted sequencing of 10ng (Table 1). DNA quality measured by DNA Integrity Number could be calculated in 35 (85%) cases with a mean of 8.9, where >7 is acceptable for sequencing (Table 1). Sequencing results of adenocarcinoma/NSCLC-NOS cases show mutations in EGFR in 6, KRAS in 8, BRAF in 1 case. Wild type was demonstrated in 6 cases. Molecular analysis of the corresponding study samples is proceeding. Table 1. DNA quantity and quality Histological subtype
Cases, n (%)
Mean DNA Mean DNA quantity Integrity (mg) Number (DIN)
Adenocarcinoma/ 25 (61.0) 3.83 NSCLC-NOS Squamous cell carcinoma 10 (24.4) 2.65 Small cell lung carcinoma 5 (12.2) 5.28 Carcinoid 1 (2.4) 16.24 Overall 41 4.03
8.8 9.0 9.0 9.1 8.9
Conclusion: A single EBUS-TBNA yields DNA of quantity and quality sufficient for molecular analysis, and is expected to be adequate for lung cancer genotyping. Keywords: EBUS-TBNA, lung cancer, Molecular
MA05.05 Genomic Profiles of Lung Cancer Associated with Idiopathic Pulmonary Fibrosis
Vol. 12 No. 1S
standardized consensus. However, despite recent progress in the understanding of pathogenesis and the treatment of LC in general population based on the advances in molecular genomics, the pathogenesis or molecular profiles of IPF-LC has been largely unknown to date. Methods: We assessed genomic profiles of IPF-LC using targeted exome-sequencing (OncoPanel version 2) in 35 matched tumor/normal pairs surgically resected between 2004 and 2014. Germline and somatic variant calling were performed using GATK HaplotypeCaller and MuTect with GATK SomaticIndelocator, respectively. Copy number analysis was conducted using CNVkit with focal events determined by GISTIC 2.0, and pathway analysis (KEGG) using DAVID. Results: Germline mutations in TERT (rs2736100,n¼33) and CDKN1A (rs2395655,n¼27) linked with IPF risk were detected in most samples. A total of 410 somatic mutations were identified with an average of 11.7 per tumor including 69 synonymous, 177 missense, 17 nonsense, 1 nonstop, 11 splice-site mutations, and 135 small coding indels. Spectra of the somatic mutations revealed predominant C/T transitions despite extensive smoking histories across most study subjects, suggesting more associations with APOBEC3B-related mutagenesis in the process of IPF-LC development, rather than smoking. TP53 (22/35,62.9%) and BRAF (6/35,17.1%) genes were found significantly mutated in IPF-LC. Recurrent focal amplifications in 3 chromosomal loci (3q26.33, 7q31.2, and 12q14.3), and 9p21.3 deletion were identified, and genes associated with JAK-STAT signaling pathway were significantly amplified in IPF-LC (P¼0.012). Conclusion: IPF-LC is genetically characterized by the presence of somatic mutations reflecting viral and immune-related mutagenic processes in the background of specific germline mutations, and is associated with potentially targetable alterations such as BRAF mutations. Keywords: idiopathic pulmonary fibrosis, genomic profile, lung cancer
Ji An Hwang, Deokhoon Kim, Soo Hyun Bae, Sung-Min Chun, Joon Seon Song, Mi Young Kim, Jin Woo Song, Woo Sung Kim, Jae Cheol Lee, Sojung Park, Hyeong Ryul Kim, Chang-Min Choi, Se Jin Jang Asan Medical Center, Seoul/Korea, Republic of
MA05.06 Diagnosis of Chronic Obstructive Pulmonary Disease in Lung Cancer - A Population Based Study
Background: Idiopathic pulmonary fibrosis (IPF) is associated with an increased risk of lung cancer (LC) independent of the effect of cigarette smoking. The prognosis of IPF-associated LC (IPF-LC) is known to be worse than the lone IPF or LC mainly due to the complications accompanying LC treatment with no established or
John Goffin,1 Grace Tang,2 Gregory Pond,2 Sophie Corriveau3 1Oncology, Juravinski Cancer Centre, Hamilton/ON/Canada, 2Oncology, Ontario Clinical Oncology Group, McMaster University, Hamilton/ON/ Canada, 3Medicine, St. Joseph’s Hospital, Hamilton/ON/ Canada