Retrospective Multicenter Study Investigating the Role of Targeted Next-Generation Sequencing of Selected Cancer Genes in Mucinous Adenocarcinoma of the.

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Retrospective Multicenter Study Investigating the Role of Targeted Next-Generation Sequencing of Selected Cancer Genes in Mucinous Adenocarcinoma of the Lung Luisella Righi, MD, Simona Vatrano, BSc, Federica Di Nicolantonio, PhD, Federica Massa, MD, Giulio Rossi, MD, Alberto Cavazza, MD, Marco Volante, MD, Arianna Votta, MLT, Stefania Izzo, MLT, Marco Lo Iacono, BSc, Francesco Ardissone, MD, Massimo Di Maio, MD, Silvia Novello, MD, Giorgio Vittorio Scagliotti, MD, Mauro Papotti, MD Journal of Thoracic Oncology Volume 11, Issue 4, Pages 504-515 (April 2016) DOI: 10.1016/j.jtho.2016.01.004 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Representative morphological patterns of 54 mucinous adenocarcinoma (ADC) (hematoxylin and eosin stains). (A) Pure invasive mucinous ADC (mucinous features ≥90%); (B) Mixed invasive mucinous ADC with up to 50% nonmucinous ADC component; (C) mucinous ADC with abundant extracellular mucin (≥10% of the tumor); (D) CPA showing mucus pools lined by columnar tumor cells; (E) Mucinous ADC with tuft growth (insert shows high-power field of bunches or small clusters of neoplastic mucinous cells attached to the alveolar wall); (F) Signet ring cells component (cells with large intracellular mucin drops and peripheral nuclei displaced toward one end of the cytoplasm). Journal of Thoracic Oncology 2016 11, 504-515DOI: (10.1016/j.jtho.2016.01.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 Total of genetic variations in 52 mucinous ADC. (A) Total genetic variations identified (namely, nonsense, nonsynonymous likely germinal, nonsynonymous likely somatic, and synonymous alterations) for each sequenced tumor in exonic or regulatory regions. (B) Distribution of nucleotide changes. Syn, synonymous; LG, likely germinal; LS, likely somatic. Journal of Thoracic Oncology 2016 11, 504-515DOI: (10.1016/j.jtho.2016.01.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Distribution of tumor-specific somatic nonsynonymous mutations. (A) Heatmap of the tumor-specific somatic mutations identified for 52 mucinous ADC samples in each gene clustered according to specific signaling pathways (a sample was considered to harbor a complex mutation when an InDel was detected concomitant with point mutations; RTK, receptor tyrosine kinases). (B) Histogram of the number of sample for each mutated gene. Journal of Thoracic Oncology 2016 11, 504-515DOI: (10.1016/j.jtho.2016.01.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Kaplan-Meier survival curves for patients segregated according to the number of nonsynonymous likely somatic alterations. Overall survival in tumors with a mutation count of at least 2 (n = 29) compared with tumors with one or no mutations (n = 23) (HR = 0.21, 95% confidence interval: 0.08–0.54, log-rank p < 0.001). Journal of Thoracic Oncology 2016 11, 504-515DOI: (10.1016/j.jtho.2016.01.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Supplementary Figure 1 Journal of Thoracic Oncology 2016 11, 504-515DOI: (10.1016/j.jtho.2016.01.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Supplementary Figure 2 Journal of Thoracic Oncology 2016 11, 504-515DOI: (10.1016/j.jtho.2016.01.004) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions