Normalization of MET CN alterations

For each sample, adjusted copy number (adCN) was calculated as the absolute CN subtracted by 2, which was defined as the normal CN, divided by tumor purity, and the addition of 2 from the resulting quotient using the following formula [Eq. 1]:

Absolute or non-adjusted copy number (non-adCN) was defined as the CN output from the segmentation algorithm used to call CN alterations. Tumor purity for each tissue sample was calculated using the maximum mutant allele fraction (maxMAF) multiplied by 2 based on the assumption that mutations are heterogeneous. MaxMAF was defined as the highest mutant allele fraction among all the mutations detected from a single sample. The maxMAF for tissue samples should meet the following criteria: not higher than 50%, and no CN alterations on the genes selected. If the maxMAF could not be determined, the tumor cell percentage determined by hematoxylin-eosin staining of the FFPE tissue samples evaluated by trained histologists were used. Tissue samples not meeting the criteria for tumor purity, tumor percentage and maxMAF were excluded from the analysis. Tumor purity in plasma cfDNA was determined by the maxMAF multiplied by 2. The maxMAF for cfDNA should meet following criteria: greater than 2% and not exceeding 50%, and no CN alterations on the genes selected in the paired tissue sample. Plasma samples that did not meet the criteria for tumor purity and maxMAF were excluded from the analysis.