Figure legends
Figure 1. Study scheme of patient cohort. Patients across 12 cancer types went through targeted sequencing as a part of clinical care from May 2017 to October 2019 were included for further analysis. NGS, next generation sequencing; NSCLC, non-small cell lung cancer; HLA-I LOH, loss of heterozygosity in human leukocyte antigen class I locus.
Figure 2. Overview of the occurrence of HLA-I LOH in Chinese cancer patients. A. The consistency in HLA-I LOH analysis of 1021-gene panel and whole-exome sequencing (WES).B. Landscape of HLA-I LOH in Chinese patients with advanced cancer. C. The incidence of HLA-I LOH across cancer types. There is an enrichment for HLA-I LOH in squamous cell carcinoma.D. The occurrence of HLA-I LOH in NSCLC cohort. There is a significant difference in the incidence of HLA-I LOH between LUAD and LUSC in both early-stage NSCLC (24/88 [27.3%] of LUAD vs. 26/42 [61.9%] of LUSC, p<0.001) and advanced patients (162/306 [52.9%] of LUAD vs. 156/251 [62.2%] of LUSC, p=0.029).E. Status of HLA-I locus in advanced patients harboring HLA-I LOH. In 43.3% (293/676) patients harboring HLA-I LOH, LOH occurred simultaneously at all three HLA class-I loci (HLA-A, B, C).
Figure 3. The relationship between HLA-I LOH and genomic instability. A. The tumor mutation burden (TMB) level of HLA-I LOH group is significantly higher than that of HLA stable group (median TMB 6.72 vs. 5.76, p<0.0001, Mann-Whitney test), indicating genomic instability in patients harboring HLA-I LOH. B. The TMB level of patients with LOH at one single site is significantly lower than that of patients with LOH co-occurrence at all three sites (median TMB 6.72 vs. 7.68, p=0.027, Mann-Whitney test). C. The proportion of HLA-I LOH in MSS samples is significantly higher than that in MSI-H samples in advanced CRC patients (61/130 [46.9%] vs. 3/17 [17.6%], p=0.022). D. Consistent results were obtained in patients with other cancer types (485/967 [50.2%] vs. 5/20 [25%], p=0.026).
Figure 4. The occurrence of HLA-I LOH is related to alterations in several oncogenic signaling pathways and genes. A. The significance histogram of DDR pathways in advanced pan-cancer cohort. The alteration frequencies of CPF pathway and FA pathway in HLA-I LOH group are significantly higher than that of HLA-I stable patients. (p<0.0001, p=0.023, respectively). B. The significance histogram of 10 oncogenic signaling pathways in advanced pan-cancer cohort. Statistical results revealed that the alteration frequencies of p53 pathway, RTK/RAS pathway, Notch pathway, Hippo pathway and Nrf2 pathway in HLA LOH group are significantly higher than HLA stable group (p<0.0001, p<0.0001, p=0.032, p=0.013, p=0.003, respectively). C. Overview of alterations of 10 oncogenic signaling pathways in advanced pan-cancer cohort.D. Waterfall chart showing mutation details of patients in advanced pan-cancer cohort.
Supplementary Figure 1. Status of HLA-I locus in advanced patients harboring HLA-I LOH across different cancer types.
Supplementary Figure 2. Comparison of TMB levels between HLA-I LOH group and HLA-I stable group across different cancer types.
Supplementary Figure 3. A. When dividing TMB more finely, the relationship between HLA-I LOH and TMB is more in line with the “Goldilocks” pattern. B. Comparison of TMB levels between MSI-H group and MSS group. C. There is a decrease in the incidence of HLA-I LOH in MSI-H samples, suggesting that the incidence of HLA-I LOH may not linear correlated with TMB.
Supplementary Figure 4. A. The alteration frequencies of ten oncogenic pathways in advanced non-squamous NSCLC cohort. B.The alteration frequencies of ten oncogenic pathways in advanced LUSC cohort. C. Waterfall chart showing mutation details of patients in advanced NSCLC (LUSC and Non-SqCC NSCLC) cohort.