A comprehensive genomic analysis of 178 lung squamous cell carcinomas (SQCCs) was conducted as part of The Cancer Genome Atlas (TCGA) project. The study revealed a high mutation rate, with an average of 360 exonic mutations, 165 genomic rearrangements, and 323 copy number alterations per tumor. Mutations in TP53 were found in nearly all samples, and previously unreported loss-of-function mutations in the HLA-A gene were identified. Key pathways altered in SQCCs included NFE2L2, KEAP1, squamous differentiation genes, phosphatidylinositol-3-OH kinase pathway genes, and CDKN2A and RBI. The study identified potential therapeutic targets in most tumors, offering new avenues for treatment. SQCCs showed a high rate of copy number alterations, with a mean of 323 segments, higher than other TCGA projects. These alterations included focal and broad somatic copy number alterations (SCNAs), with a mean of 47 focal and 23 broad events per tumor. The study also identified mutations in genes such as TP53, CDKN2A, PTEN, PIK3CA, KEAP1, MLL2, HLA-A, NFE2L2, NOTCH1, and RB1. These mutations were associated with significant functional effects. The study also identified four subtypes of SQCCs based on gene expression profiles: classical, basal, secretory, and primitive. These subtypes were associated with different genomic alterations and had distinct biological characteristics. The classical subtype was characterized by alterations in KEAP1, NFE2L2, and PTEN, as well as pronounced hypermethylation and chromosomal instability. The 3q26 amplicon was present in all subtypes, but was most characteristic of the classical subtype. The study also identified CDKN2A inactivation in 72% of SQCCs, with various mechanisms including epigenetic silencing, inactivating mutations, exon 1β skipping, and homozygous deletion. The study found that CDKN2A inactivation was associated with different subtypes and had significant functional consequences. The study identified potential therapeutic targets in most SQCCs, with mutations in tyrosine kinases, serine/threonine kinases, phosphatidylinositol-3-OH kinase (PI(3)K) catalytic and regulatory subunits, nuclear hormone receptors, G-protein-coupled receptors, proteases, and tyrosine phosphatases. These mutations were associated with significant functional effects and could be targeted for therapy. The study also identified alterations in key oncogenic pathways, including PI(3)K/AKT, receptor tyrosine kinase (RTK), and RAS. These alterations were associated with different subtypes and hadA comprehensive genomic analysis of 178 lung squamous cell carcinomas (SQCCs) was conducted as part of The Cancer Genome Atlas (TCGA) project. The study revealed a high mutation rate, with an average of 360 exonic mutations, 165 genomic rearrangements, and 323 copy number alterations per tumor. Mutations in TP53 were found in nearly all samples, and previously unreported loss-of-function mutations in the HLA-A gene were identified. Key pathways altered in SQCCs included NFE2L2, KEAP1, squamous differentiation genes, phosphatidylinositol-3-OH kinase pathway genes, and CDKN2A and RBI. The study identified potential therapeutic targets in most tumors, offering new avenues for treatment. SQCCs showed a high rate of copy number alterations, with a mean of 323 segments, higher than other TCGA projects. These alterations included focal and broad somatic copy number alterations (SCNAs), with a mean of 47 focal and 23 broad events per tumor. The study also identified mutations in genes such as TP53, CDKN2A, PTEN, PIK3CA, KEAP1, MLL2, HLA-A, NFE2L2, NOTCH1, and RB1. These mutations were associated with significant functional effects. The study also identified four subtypes of SQCCs based on gene expression profiles: classical, basal, secretory, and primitive. These subtypes were associated with different genomic alterations and had distinct biological characteristics. The classical subtype was characterized by alterations in KEAP1, NFE2L2, and PTEN, as well as pronounced hypermethylation and chromosomal instability. The 3q26 amplicon was present in all subtypes, but was most characteristic of the classical subtype. The study also identified CDKN2A inactivation in 72% of SQCCs, with various mechanisms including epigenetic silencing, inactivating mutations, exon 1β skipping, and homozygous deletion. The study found that CDKN2A inactivation was associated with different subtypes and had significant functional consequences. The study identified potential therapeutic targets in most SQCCs, with mutations in tyrosine kinases, serine/threonine kinases, phosphatidylinositol-3-OH kinase (PI(3)K) catalytic and regulatory subunits, nuclear hormone receptors, G-protein-coupled receptors, proteases, and tyrosine phosphatases. These mutations were associated with significant functional effects and could be targeted for therapy. The study also identified alterations in key oncogenic pathways, including PI(3)K/AKT, receptor tyrosine kinase (RTK), and RAS. These alterations were associated with different subtypes and had