Genomic landscape of ground glass opacities (GGOs) in East Asians

Abstract

Background: Understanding the genomic landscape of early-stage lung adenocarcinoma (LUAD) may provide new insights into the molecular evolution in the early stages of LUAD. Methods: Through sequencing of 79 spatially distinct regions from 37 patients with ground glass opacities (GGOs), we provided a comprehensive mutational landscape of GGOs, highlighting the importance of ancestry differences. Results: Our study had several interesting features. First, epidermal growth factor receptor (EGFR), BRAF (v-RAF murine sarcoma viral oncogene homologue B1), and ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2, also known as HER2) were more frequently mutated in our study, which supports the notion that EGFR is considered to be a major driver and tends to drive the occurrence of LUAD. Second, Signature 1, Signature 3, and Signature 6 were identified in patients with GGOs. Our results further suggested that Signature 1 was more prominent among early mutations. Third, compared with LUADs, GGOs exhibited significantly lower levers of arm-level copy number variation (CNV)-which alter the diploid status of DNA, and lower focal CNVs.Conclusions: In our study, 79 samples of patients were included to analyze the GGO gene profile, revealing the genetic heterogeneity of GGO in East Asian population, and providing guidance for prognosis analysis of GGO patients by comparison with LUAD. Our study revealed that GGOs had fewer genomic alterations and simpler genomic profiles than LUADs. The most commonly altered processes were related to the receptor tyrosine kinase (RTK)/Ras/phosphatidylinositol-3-kinase (PI3K) signaling pathways in GGOs, and EGFR alterations were the dominant genetic changes across all targetable somatic changes.

Genomic Profiling of Radiation-Induced Sarcomas Reveals the Immunologic Characteristics and Its Response to Immune Checkpoint Blockade

“…The R packages nonnegative matrix factorization and MutationalPatterns were used to discover the mutational patterns of RIS ( 36–38 ). The resulting signature contribution proportions were further used to cluster samples by using all known COSMIC signatures ( https://cancer.sanger.ac.uk/cosmic/signatures ).…”

Multidimensional biological characteristics of ground glass nodules

“…In the preinvasive phase, EGFR is the most common gene mutation in GGNs, followed by ERBB2 , RBM10 , and KRAS mutations ( 12 – 14 , 27 , 28 , 30 , 31 , 33 – 35 ). The exon 21 L858R mutation is reportedly the most common EGFR mutation among GGNs, followed by exon 19 deletion mutations ( 30 , 33 ).…”

“…EGFR , ERBB2 , NRAS , and BRAF mutations contribute to the early clonal genomic events in lung ADC. In contrast, mutations in TP53 and genes associated with cell migration, gap junctions, and metastasis (such as FRG1, DOCK7, SH3BP1 , and GJA1 ) may be late events that occur during subclonal diversification and tumor progression ( 12 , 14 ). Similar proportions of EGFR mutations were observed in IAC and MIA/AIS, whereas TP53 was mutated in IAC at a much higher proportion than in MIA/AIS ( 12 ).…”

Comprehensive characterization of genomic and radiologic features reveals distinct driver patterns of RTK/RAS pathway in ground‐glass opacity pulmonary nodules

“…More than 70% of AIS, MIA or IAC patients carry at least one cancer‐related gene mutation in the RTK/RAS pathway, especially in East Asian lung cancer patients 9‐11 . Increasing evidence supports that the activation of RTK/RAS pathway could be an early event in LUAD tumorigenesis 12,13 . However, the associations between the common driver genes in RTK/RAS pathway and radiologic features in GGO‐associated LUAD remain poorly defined.…”

“… 9 , 10 , 11 Increasing evidence supports that the activation of RTK/RAS pathway could be an early event in LUAD tumorigenesis. 12 , 13 However, the associations between the common driver genes in RTK/RAS pathway and radiologic features in GGO‐associated LUAD remain poorly defined.…”