SCLC1 gene
The SCLC1 gene is located on chromosome 3 and plays a significant role in the development of small-cell lung cancer (SCLC), a highly aggressive form of lung cancer that accounts for about 14% of lung cancer cases. This gene's expression is particularly noted in individuals with lung cancer and is influenced by factors such as cigarette smoking, which is linked to approximately 90% of lung cancer cases. Inheritance of SCLC1 is autosomal dominant, meaning that individuals carrying this gene have an increased predisposition to develop lung cancer, though multiple genetic and environmental factors must interact for cancer to manifest.
SCLC is characterized by various genetic abnormalities, including deletions on chromosome 3, which are commonly associated with lung cancer progression. Loss of heterozygosity at various chromosomal loci further complicates the genetic landscape of this disease. Recent research highlights the potential for new treatments targeting the SCLC1 gene, specifically by inhibiting chromatin remodeling complexes associated with it, which may reduce tumor growth. Given its strong connection to lung cancer, understanding the SCLC1 gene is crucial for advancing diagnosis, treatment, and prognosis in affected individuals.
SCLC1 gene
SIGNIFICANCE: The SCLC1 gene is expressed in cells and tissues of individuals with lung cancer, particularly small-cell cancer of the lung. Interactions between cigarette smoking and acquired chromosomal abnormalities facilitate expression of this gene.
Small-Cell Lung Carcinoma
According to the American Lung Association, lung cancer is the most common cancer worldwide and the most common cause of cancer deaths in the United States. There are two main types of lung cancer: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), with the distinction based primarily on the appearance of the cancer cells under the microscope. SCLC accounts for approximately 14 percent of all lung cancer diagnoses. It is highly aggressive and is associated with poor prognosis, as metastases are generally already present at the time of diagnosis. In 2014 the American Cancer Society reported that the five-year survival rate for SCLC cases diagnosed between 2003 and 2009 was only 6 percent, compared to 18 percent for NSCLC. Tobacco smoke is the most common carcinogen associated with SCLC, with only a vanishingly small percentage of cases occurring in patients who have never smoked.
Chromosome Location and Inheritance
The SCLC1 gene, also known as SCLC or SCCL, is located on chromosome 3, between bands 21 and 23 of the short arm of this chromosome (denoted 3p23–p21). Inheritance of this gene is autosomal dominant. Individuals who carry the SCLC1 gene are predisposed to develop lung cancer, although a combination of several genetic defects and environmental factors is required before cancer develops. SCLC and other types of lung cancer are examples of cancer induced by external factors, such as carcinogens in cigarette smoke, but associated with specific chromosomal changes.
Molecular Abnormalities Associated with SCLC
Although SCLC is strongly tied to cigarette smoking, with an estimated 90 percent of lung cancers caused by smoking, a number of genetic abnormalities are also observed in lung cancer cells. Some are markers of disease progression, while others play direct roles in lung cancer development. Lung cancers are characterized by multiple gene alterations, such as amplification of oncogenes and deletions or mutations in tumor-suppressor genes during disease progression. Common chromosomal abnormalities associated with lung cancer include deletions on the short arms of chromosomes 3 [del(3p)] and 9 [del(9p)]. The most frequent genetic mutation associated with SCLC is deletion of a region on the short arm of chromosome 3 in an area that contains several genes potentially associated with lung cancer. Specifically, deletion of alleles located on bands 14 through 25—that is, 3p(14–25)—are associated with lung cancer development.
Loss of Heterozygosity and Tumor-Suppressor Genes
In hereditary cancer syndromes that give individuals a predisposition to certain forms of cancer, individuals are heterozygous, which means they have at least one gene pair with different alleles. The other allele of that pair is normal, so the disease is not immediately expressed. If the normal suppressive gene that inhibits expression of the disease phenotype is lost, such as through chromosomal deletion, a condition called loss of heterozygosity occurs. Loss of heterozygosity at multiple chromosomal loci has been identified in lung cancer, along with changes in and oncogenes. Most small-cell lung carcinomas are associated with large deletions in segments of 3p, leading to loss of heterozygosity at numerous loci, including many potential tumor-suppressor genes.
Impact
The SCLC1 gene is associated with lung cancer development and is known as a cancer-predisposing gene. A specific acquired chromosomal abnormality, a deletion on the short arm of chromosome 3, is associated with SCLC. Many inherited cancer syndromes exhibit intricate interactions with environmental factors. Interactions between cigarette smoking and a predisposition to developing lung cancer are documented. Susceptibility to many inherited cancer syndromes is now detectable through genetic screening, and advances in molecular genetics associated with some forms of lung cancer can lead to new approaches to diagnosis, treatment, and prognosis. In 2024, researchers at Northwest Medicine discovered that inhibiting a chromatin remodeling complex associated with the SCLC1 gene had the potential to decrease tumor growth. This discovery has the potential to be developed into future medical treatments for lung cancer.
Key Terms
- alleleone member of a pair of different forms of a gene at a specific locus
- autosomal dominantthe presence of one abnormal gene allows expression of that gene
- chromosomal deletionchromosomal abnormality in which part of the chromosome is missing or deleted
- heterozygositydifferent alleles of a given gene at a locus
- locuslocation on a chromosome occupied by one or more genes
- loss of heterozygosityloss of alleles at numerous chromosomal loci
- oncogenetransforms a normal cell into a tumor cell when mutated or expressed
- tumor-suppressor genea gene that inhibits tumor cell growth
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