Using Whole Genome Amplification (WGA) of Low-Volume Biopsies to Assess the Prognostic Role of EGFR, KRAS, p53, and CMET Mutations in Advanced-Stage Non-

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Using Whole Genome Amplification (WGA) of Low-Volume Biopsies to Assess the Prognostic Role of EGFR, KRAS, p53, and CMET Mutations in Advanced-Stage Non- small Cell Lung Cancer (NSCLC) Elaine H. Lim, MD, PhD, Shen-Li Zhang, MD, Jia-Liang Li, PhD, Wee-See Yap, MD, Tse-Chiang Howe, MD, Bien-Peng Tan, MD, Yong- Shyan Lee, MD, Daniel Wong, MD, Kay-Leong Khoo, MD, Kar-Yin Seto, MD, Lenny Tan, MD, Thirugananam Agasthian, MD, Heng- Nung Koong, MD, John Tam, MD, Christie Tan, MD, Michael Caleb, MD, Alex Chang, MD, Alan Ng, MD, Patrick Tan, MD, PhD Journal of Thoracic Oncology Volume 4, Issue 1, Pages 12-21 (January 2009) DOI: 10.1097/JTO.0b013e3181913e28 Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 1 Detection of deoxyribonucleic acid (DNA) mutations in unamplified and whole genome amplification (WGA)-amplified genomic DNA (gDNA) extracted from surgically-resected lung tumors. Left column, Sequence chromatograms of wildtype tumors using unamplified gDNA. Middle column, Sequence chromatograms of mutation-bearing tumors using unamplified gDNA. Right column, Sequence chromatograms of mutation-bearing tumors, same as in the middle column, but using WGA-amplified gDNA. Identity numbers of the mutation-bearing tumors are listed on the right. A, epidermal growth factor receptor (EGFR) exon 19: the start of the heterozygous in-frame deletion (delE746-A750) is indicated by the arrows. B, Kras exon 2: the heterozygous missense mutation (G12C) is indicated by the arrows. C, p53 exon 5: the start of the heterozygous in-frame deletion (delR158-Y163) is indicated by the arrows. Journal of Thoracic Oncology 2009 4, 12-21DOI: (10.1097/JTO.0b013e3181913e28) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 2 Detection of deoxyribonucleic acid (DNA) mutations in unamplified and whole genome amplification (WGA)-amplified genomic DNA (gDNA) extracted from low-volume lung biopsies. Left column, Sequence chromatograms of wildtype tumors using unamplified gDNA. Middle column, Sequence chromatograms of mutation-bearing tumors using unamplified gDNA. Right column, Sequence chromatograms of mutation-bearing tumors, same as in the middle column, but using WGA-amplified gDNA. Identity numbers of the mutation-bearing tumors are listed on the right. A, p53 exon 5: the heterozygous missense mutation (R158L) is indicated by the arrows. B, p53 exon 7: the heterozygous missense mutation (Y236stop) is indicated by the arrows. Journal of Thoracic Oncology 2009 4, 12-21DOI: (10.1097/JTO.0b013e3181913e28) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions

FIGURE 3 A, Overall survival of 88 non-small cell lung cancer (NSCLC) patients (survival time in days). The dotted lines indicate 95% confidence intervals. B, Survival curves of patients with and without KRAS mutations (survival time in days). C, Survival curves of patients with and without epidermal growth factor receptor (EGFR) mutations (survival time in days). Journal of Thoracic Oncology 2009 4, 12-21DOI: (10.1097/JTO.0b013e3181913e28) Copyright © 2009 International Association for the Study of Lung Cancer Terms and Conditions