Hereditary Genetics: Current Research

Somatic Genomic Alterations and Mechanisms of Genomic Instability in Lung Cancer

Kevin Gleick^* Department of Molecular and Human Genetics, Millersville University, Millersville, United States of America
^*Correspondence: Kevin Gleick, Department of Molecular and Human Genetics, Millersville University, Millersville, United States of America, Email:

Received: 03-Mar-2023, Manuscript No. HGCR-23-20822; Editor assigned: 06-Mar-2023, Pre QC No. HGCR-23-20822 (PQ); Reviewed: 20-Mar-2023, QC No. HGCR-23-20822; Revised: 27-Mar-2023, Manuscript No. HGCR-23-20822 (R); Published: 03-Apr-2023, DOI: 10.35248/2161-1041.23.12.237

Description

Lung Cancer (LC) remains the largest cause of cancer death. Histologically, lung cancer is divided into two subtypes: Non- Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC), which account for 85% and 15% of LC cases, respectively. Adenocarcinoma (50%) is the most common type of NSCLC, followed by squamous cell carcinoma (30%-40%) and large cell carcinoma (10%-20%). Independent of gender, age, or smoking history, adenocarcinoma is the most common subtype of NSCLC, but squamous cell and large cell carcinoma are closely associated with smokers. Although NSCLC is frequently identified as advanced metastatic disease, vascular invasion occurs frequently in the early stages, leading to recurrence and poor survival [1-3]. Surgery for local tumours and platinum-based chemotherapy for systemic illness are common therapies. Notwithstanding recent advancements, NSCLC remains a highly recurring cancer with a 5-year survival rate of roughly 15%. LC has hundreds of somatic mutations, copy number changes, and genome duplications, according to genomic studies. Tobacco carcinogen exposure mixed with germline genomic instability causes in a high somatic mutation rate in LC [4].

The multiple sub clonal populations obtained from a single biopsy demonstrate the considerable genetic diversity within LC malignancies. Tobacco use and DNA repair changes, for example, are extrinsic and intrinsic variables that contribute to frequent genomic abnormalities in LC. Yet, only a small percentage of smokers get cancer, emphasizing the role of germline genetic predisposition in lung carcinogenesis. When compared to other kinds of cancer, LC has a specific genetic signature. Tobacco-related lung cancer ranks second only to melanoma among malignancies with a high somatic mutational load. The high somatic mutation rate (8-10 mutations/Mb) in smokers, independent of histologic subtype, compared to less than 1 mutation/Mb in nonsmokers, confirms tobacco carcinogen causation. Furthermore, transversion rates (C-A) are unusually high in smoking-related LC, both in squamous cell carcinoma and adenocarcinoma, with the highest frequency compared to other cancer types, surpassed only by melanoma rates derived from UV light exposure, whereas transitions are more common in most cancer types. Endogenous mutational processes also result in the complex genome of LC, which exhibits frequent nonsilent mutations, copy number changes (CNA), chromosomal translocations, and genome doublings [5-7].

NSCLC initial tumours have a significant level of genetic variability. Beyond tobacco smoking, increased somatic mutational burden is related with germline polymorphisms, according to the spatial and temporal dynamics of tumour evolution. Tumor driver mutations spread unevenly and might be dominant in some clones while being missing in others. Remarkably, with chronic exposure to tobacco carcinogens, smoking-related mutations fade, and endogenous-derived mutations take over during tumour evolution [8,9]. The specific genomic profile of LC defines various molecular categories of patients and serves as the foundation for customized therapy that target driver mutations. A variety of Tyrosine Kinase Inhibitors (TKIS) have been discovered during the last decade for Epidermal Growth Factor Receptor (EGFR) mutations and Anaplastic Lymphoma Kinase (ALK) fusions, while next generation sequencing is uncovering additional molecular targets. Results from numerous sequencing experiments reveal distinct genetic landscapes based on histology type. Mutations in receptor tyrosine kinases are common in lung adenocarcinoma but uncommon in squamous or big cell carcinomas. Defective cell cycle control, involving cyclins, cyclin-dependent kinases, tumour suppressors, and oncogenes, is the key molecular mechanism generating genomic instability in LC. Because many of these proteins correlate with cancer cell growth, survival, tumorigenesis, and metastasis in preclinical models both in vitro and in vivo, and they are overexpressed and/or have prognostic value in LC patients, this represents opportunities for the development of novel biomarkers and targeted therapies [10].

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