Identifying Genetic Mutations in Retinoblastoma Cancer: A Clinical Pathway Approach

Retinoblastoma is a rare cancer of the infant retina that is diagnosed in approximately ۸,۰۰۰ children each year worldwide. It forms when both retinoblastoma gene (RB۱) alleles are mutated in a susceptible retinal cell, probably a cone photoreceptor precursor. Loss of the tumor-suppressive functions of the retinoblastoma protein (pRB) leads to uncontrolled cell division and recurrent genomic changes during tumor progression. Although pRB is expressed in almost all tissues, cone precursors have biochemical and molecular features that may sensitize them to RB۱ loss and enable tumorigenesis. Intra-arterial and intravitreal chemotherapy has emerged as promising methods to salvage eyes that, with conventional treatment, might have been lost. Life-long follow-up is warranted, as survivors of heritable retinoblastoma are at risk for developing second cancers. Defining the molecular consequences of RB۱ loss in diverse tissues may open new avenues for treating and preventing retinoblastoma and second cancers in patients with germline RB۱ mutations.Method: Genetic testing will be performed on blood samples from patients and family members, including next-generation sequencing of the RB۱ gene and whole exome sequencing. Obtaining tumor tissue samples from retinoblastoma patients often involves a multi-step process utilizing cutting-edge technology. This might involve minimally invasive procedures guided by imaging techniques. DNA is extracted from the collected tissue, and scientists extract the genetic material, Deoxyribonucleic Acid (DNA), which holds the blueprint for cells. Next-Generation Sequencing (NGS)This technique acts like a high-speed reader, deciphering a patient's DNA's entire sequence of nucleotides (the building blocks). Researchers compare this sequence to a healthy reference genome, identifying any variations or "typos" that could be mutations associated with retinoblastoma. Copy Number Variation (CNV) Analysis This method goes beyond sequencing and looks for changes in the quantity of genetic material. Researchers use sophisticated tools to detect missing sections (deletions) or extra copies (amplifications) of DNA segments, which can also contribute to retinoblastoma development. By combining these techniques, researchers can create a detailed picture of the mutational landscape in each patient's tumor. Result: The article emphasizes the critical role of genetic mutations in the RB۱ gene in shaping how retinoblastoma manifests and progresses. This approach offers two benefits: improved stratification and enhanced prognostication. By identifying specific mutations in individual patients, we can categorize them into distinct groups. This allows for the development of targeted treatment plans, tailoring therapies to the particular genetic makeup of the cancer. This knowledge enables physicians to refine treatment strategies and improve patient outcomes. By leveraging genetic information, we can move towards therapies directly targeting identified mutations, offering a more effective and less-invasive approach to combating this devastating disease. Conclusion: Early genetic screening, particularly for RB۱ mutations, enables prompt diagnosis and risk stratification, facilitating timely intervention and improved outcomes. Identifying specific genetic alterations beyond RB۱ provides valuable prognostic information and guides personalized treatment strategies. Emerging technologies, such as liquid biopsy and single-cell sequencing, show promise in non-invasive disease progression and treatment response monitoring. Long-term follow-up guided by genetic risk factors enables more effective surveillance for secondary malignancies in heritable retinoblastoma survivors.

کلیدواژه ها:

Retinoblastoma ، Genetic mutations ، Pediatric cancer ، Clinical pathway