Additional file 1 of The enrichment of Fanconi anemia/homologous recombination pathway aberrations in ATM/ATR-mutated NSCLC was accompanied by unique molecular features and poor prognosis
Creators: name: Wei, Wei
name: Shi, Fangfang
name: Xu, Yang
name: Jiao, Yang
name: Zhang, Ying
name: Ou, Qiuxiang
name: Wu, Xue
name: Yang, Lingyi
name: Lai, Jinhuo
Publisher: name: figshare
Year: 2024
Subjects: subject: Biophysics
subject: Biochemistry
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Molecular Biology
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology
subject: Computational Biology

description: Additional file 1: Figure S1. The workflow of the study cohort and external cohort. Figure S2. PIKK pathogenic mutations were associated with higher mutational loads in NSCLC. (A) The TMB in PIKK-Mut and PIKK-WT NSCLC patients from the external cohort. (B) The comparison of TMB between different PIKK mutational status and histological subtypes in the external cohort. (C) The MSI in PIKK-Mut and PIKK-WT SCC patients from the study cohort. (D) The comparison of CIS stratified by both the PIKK mutational status and histological subtypes in the study cohort. (E) The oncoprint plot of NSCLC patients without any PIKK mutations from the study cohort. CNV, copy-number variation. Figure S3. The CNV enriched in PIKK-mutated patients. (A, B) The comparison of chromosome arm CNV (A) and gene-level CNV (B) between PIKK-mutated and PIKK-WT patients from the study cohort. The analyses were done using Fisher’s exact test, and all multiple comparisons were corrected by the Benjamini &amp; Hochberg approach. Figure S4. The relationship between FA/HR mutations and demographic/clinical characteristics in the study cohort. (A-C) The age (A), sex (B), and histological subtype (C) differences in PIKK-mutated patients with different FA/HR mutational statuses. Figure S5. Patients with both PIKK and FA/HR mutations were associated with more nucleotide-level alterations. (A-C) The comparison of TMB (A), CIS (B), and MSI (C) in PIKK-mutated NSCLC patients with different FA/HR mutational statuses. Figure S6. PIKK and FA/HR co-mutations were associated with higher nucleotide-level changes and worse prognosis. (A, B) The comparison of TMB in NSCLC patients with different PIKK and FA (A) or HR (B) mutational statuses in the study cohort. (C, D) The comparison of CIS in NSCLC patients with different PIKK and FA (C) or HR (D) mutational statuses in the study cohort. (E, F) The comparison of MSI frequency in NSCLC patients with different PIKK and FA (E) or HR (F) mutational statuses in the study cohort. (G-I) The comparison of TMB in NSCLC patients with different PIKK and FA/HR mutational statuses in the external cohort. (J, K) Kaplan-Meier curve of overall survival in NSCLC patients from the external cohort in strata of different PIKK and FA (J) or HR (K) mutational statuses. Figure S7. CNV and pathways enriched in ATM-mutated versus ATR-mutated patients. (A, B) The gene-level CNV (A) and chromosome arm-level CNV (B) that were enriched in ATM-mutated or ATR-mutated patients. The analyses were done using Fisher’s exact test, and all multiple comparisons were corrected by the Benjamini &amp; Hochberg approach. (C, D) The gene ontology analysis of mutated genes enriched in ATM-mutated patients (C) or ATR-mutated patients (D). Figure S8. The association of ATM/ATR and FA/HR co-mutations and various molecular and clinical characteristics. (A, B) The comparison of TMB in NSCLC patients from the study cohort who were stratified by different ATM/ATR and FA (A) or HR (B) mutational statuses. (C-E) The comparison of TMB in NSCLC patients from the external cohort who were stratified by different ATM/ATR and FA/HR mutational statuses. (F, G) The comparison of CIS in NSCLC patients from the study cohort who were stratified by different ATM/ATR and FA (F) or HR (G) mutational statuses. (H, I) The comparison of MSI frequency in NSCLC patients from the study cohort who were stratified by different ATM/ATR and FA (H) or HR (I) mutational statuses. (J) Kaplan-Meier curve of overall survival in NSCLC patients from the external cohort in strata of different ATM/ATR and FA mutational statuses. Figure S9. The proposed tumorigenesis model in DDR-mutation driven NSCLC tumors. Table S1. The ATM/ATR pathological mutations detected in the study cohort. Table S2. Demographic characteristics of the 499 NSCLC patients in the study cohort. Table S3. The ATM/ATR pathological mutations in the external cohort. Table S4. Demographic characteristics of the 2,727 NSCLC patients in the external cohort. Table S5. The list of mutated genes that were enriched in PIKK-mutated patients by at least 2 fold. Table S6. The list of mutated genes that were enriched in ATM or ATR by at least two folds.