Extended Data Fig. 6: Copy number analyses for NSCLC tumors in cohort 1. | Nature Cancer

Extended Data Fig. 6: Copy number analyses for NSCLC tumors in cohort 1.

From: Multimodal genomic features predict outcome of immune checkpoint blockade in non-small-cell lung cancer

Extended Data Fig. 6

Given that deletions in IFN-ɣ genes have been described as a potential mechanism of intrinsic resistance to immunotherapy, we investigated whether there is an enrichment in IFN-ɣ related gene copy number variation in non-responding tumors. (a) A cluster of IFN-ɣ related genes (IFNE, IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA8, IFNA14, IFNA21, IFNW1 and IFNB1) is located on chromosome 9 (p21.3), in close proximity to the CDKN2A locus. (b) The locus that contains both the IFN-ɣ related genes and CDKN2A was frequently found to be deleted; an example of such homozygous deletion is shown for case CGLU262. The vertical axes denote the relative copy ratio (log2 scale), and the integer copy number levels assigned to genomic bins (circles) and segments. Purple and green boxes mark the coordinates of IFN gene cluster and CDKN2A, respectively. (c) The frequency of homozygous deletions in IFNE, IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA8, IFNA14, IFNA21, IFNW1 and IFNB1 was similar in responding and non-responding tumors and more importantly, these deletions co-occurred with CDKN2A loss in 86% of the cases, whereas CDKN2A deletions also occurred independently. Given that, CDKN2A and the group of IFN-ɣ pathway genes lie on chromosome 9p within a span of 917 Kb, IFN-ɣ deletions may be passengers in the setting of a driver CDKN2A deletion. Seventy five tumors had evaluable copy number estimates (Methods). (d) A genome-wide analysis of copy number profiles revealed genomic regions with copy number gains and losses and was used to determine the extent of tumor aneuploidy. The relative copy ratio (LogR) values quantifying the abundance of each genomic region compared to the genome average (ploidy) are shown after correction for tumor purity in responding (N=33 tumors) and non-responding tumors (N=41 tumors). Red and blue shades indicate copy gains and losses, respectively, whereas white marks copy neutral regions. There was no significant difference in the degree of aneuploidy assessed by the fraction of genome with allelic imbalance between the two groups (Mann Whitney U test p=0.367, FDR-corrected p=0.65). We defined response as durable clinical benefit (DCB) if complete, partial response or stable disease was achieved with a duration >6months. P values are based on two-sided testing. CAN; copy number aberration, NDB; non durable clinical benefit.

Source data

Back to article page