Extended Data Fig. 7: Malignant epithelial cells harboring LOY exhibited higher genomic instability.
From: Concurrent loss of the Y chromosome in cancer and T cells impacts outcome
a. Sequencing depth of Whole Exome Sequencing (WES) data from CRISPR Y-KO and Y-Scr MB49 cells. b. LOY gene phenotype scores in LOYBR (n = 74) versus WTYBR (n = 147) TCGA Bladder Cancer (BLCA) samples. Data are presented as mean ± s.e.m. and significance was assessed based on two‐sided Wilcoxon rank sum tests. c. LOY gene phenotype scores across multiple cancer types in the TCGA dataset. Significant LOY gene phenotype trends were observed in Lung Adenocarcinoma (LUAD), Pancreatic Adenocarcinoma (PAAD), and Stomach Adenocarcinoma (STAD), with variable significance across other cancers. ACC (LOYBR, n = 14; WTYBR, n = 14), BLCA (LOYBR, n = 74; WTYBR, n = 147), BRCA (LOYBR, n = 0; WTYBR, n = 8), CHOL (LOYBR, n = 6; WTYBR, n = 10), COAD (LOYBR, n = 70; WTYBR, n = 85), DLBC (LOYBR, n = 7; WTYBR, n = 13), ESCA (LOYBR, n = 82; WTYBR, n = 33), GBM (LOYBR, n = 4; WTYBR, n = 85), HNSC (LOYBR, n = 143; WTYBR, n = 129), KICH (LOYBR, n = 20; WTYBR, n = 17), KIRC (LOYBR, n = 132; WTYBR, n = 184), KIRP (LOYBR, n = 168; WTYBR, n = 35), LAML (LOYBR, n = 4; WTYBR, n = 59), LGG (LOYBR, n = 16; WTYBR, n = 246), LIHC (LOYBR, n = 64; WTYBR, n = 150), LUAD (LOYBR, n = 77; WTYBR, n = 106), LUSC (LOYBR, n = 151; WTYBR, n = 133), MESO (LOYBR, n = 17; WTYBR, n = 44), PAAD (LOYBR, n = 44; WTYBR, n = 48), PCPG (LOYBR, n = 1; WTYBR, n = 72), PRAD (LOYBR, n = 9; WTYBR, n = 448), READ (LOYBR, n = 33; WTYBR, n = 30), SARC (LOYBR, n = 22; WTYBR, n = 63), SKCM (LOYBR, n = 93; WTYBR, n = 156), STAD (LOYBR, n = 137; WTYBR, n = 75), TGCT (LOYBR, n = 26; WTYBR, n = 94), THCA (LOYBR, n = 4; WTYBR, n = 123), THYM (LOYBR, n = 2; WTYBR, n = 56), UVM (LOYBR, n = 22; WTYBR, n = 22), d-e. Pathway enrichment of the running enrichment scores (top), and positions of pathway genes ordered by log fold change (bottom) in Gene Set Enrichment Analysis (GSEA) comparing CRISPR Y-KO MB49 cells with CRISPR Y-Scr MB49 cells. NES, normalized enrichment score. NES > 0 indicate the pathway is enriched in Y-KO cells, otherwise in Y-Scr cells. f-g. Stacked bar plots showing counts of Single Nucleotide Polymorphisms (SNPs, f) and Insertion and Deletions (Indels, g) in different genomic regions. CDS, coding DNA sequence. h. Ratio of mutation counts (SNPs and Indels) between CRISPR Y-KO cells and Y-Scr MB49 cells across different chromosomes.
