Researchers analyze the mutation landscape of TMB-Hohen intestinal cancer tumors

Colon cancer (CRC), a kind of cancer that affects the colon and the rectum, is one of the main causes of cancer -related deaths worldwide. CRC's mutation landscape is well characterized and shows important pathogenic genetic anomalies that drive carcinogenesis (cancer development) and the progression of the disease. In addition, a gradual colorectal carcinogenic model was proposed, in which normal epithelial cells to adenoma (non -cancer -like tumor) and then pass to carcinoma (cancer tumor) if they record genetic mutations one after the other.

Mutations in APCPresent TP53Present CrasAnd Pik3ca At CRC patients, genes have often been reported and has shown that they drive tumor formation. However, the frequency of these mutations varies with the position of the tumor; APC And TP53 Mutations are more common in the left -wing colon cancer, while Cras Mutations are more common in the case of right -sided colon cancer. In addition, the place of the tumor also influences its morphology, immune movement filtration, forecast, metastasis and treatment reaction, which indicates that the mechanisms that are underlying are probably on site.

Recently, BRAF Mutations were involved in the development of tumors with a low frequency of APCPresent TP53Present CrasAnd Pik3ca Mutations. It is known that these tumors develop genetic and epigenetic mechanisms about alternative genetic and epigenetic mechanisms, which are also known as “jagged path”. An alternative carcinogenesis model based on BRAF Mutations, microsatellite instability (MSI) and methylator phenotype status of CPG Island were proposed, although the underlying mechanisms are unknown.

To bridge this gap, A Team of Researchers LED by Dr. Hideyuki Saya, Director of the Oncology Innovation Center, Fujita Health University, Japan, Including Associate Professor Tetsuya Takimoto, Dr. Yuko Chikaishi, and Dr. Hiroshi Matsuoka, Analyzed Crc Tumors With High Tumor Mutation Burden (TMB) to Characterize BRAF-Associated mutations and decipher your role in carcinogenesis of tumors, which are missing important drivers. Give further insights into your work, in a study published in Cancer science On January 16, 2025, Dr. “We have observed that CRCs, which arise in the right and left large intestine, differentiate both in their oncogenic mechanisms and in biological properties. As a result, the treatment approaches should also differ. Generalis analysis for each cancer type can lead to the selection of treatment and help to improve the results of patients with CRC.”

The researchers carried out a targeted exom sequence in order to analyze a gene gene sequencing technology for the analysis of protein coding regions of the genome using tumor samples received by 150 patients with CRC. They used a proprietary in-house cancer genome analysis system and evaluated the type and frequency of gene mutations based on TMB, MSI and Tumor. 14 tumors were classified as a TMB high. Remarkably, there were 12 out of 14 tumors in the right colon and had a high BRAF Mutation frequency and high MSI. Furthermore, a high TMB was significantly associated with a older age and the MSI high status.

In addition, mutations in DNA damage response -reaction converter such as ATM And Pole, and non -agreement repair path genes MSH2 And MSH6, were often and significantly connected to a high TMB. Mutation signature analysis showed that these mutations are likely to precede BRAF Mutations associated with the activation of the jagged path, which indicates their possible role in early carcinogenesis.

During TMB-high tumors did not harmonize APCPresent TP53or Cras MutationsPresent The analysis revealed mutations in genes for paths that with these important oncogenic contexts, including mutations in receptor-tyrosineinase (RTK)-Ras-Pathway gene, and BRAFPhosphatidylinositol 3-kinase (Pi3k) Pathway gene, Pten, and notch Pathway gene; These mutations are likely to contribute to survival and maintaining the tumor.

Overall, these results suggest that TMB-high CRC tumors are likely to result from a heterogeneous population of cells, which distinguishes numerous gene mutations from the driver-onkogenic. The researchers thus speculate that these TMB-high tumors rely on alternative gene mutations that can react well to targeted treatments and immunotherapies. Dr. Saya share his final thoughts, says Dr. Saya. “Currently, the cancer -good is only carried out for a subgroup of cancer patients. In the future, however, it could certainly become a standard test for all types of cancer in order to better understand its genomic properties and to develop suitable treatment strategies.”

The team is currently optimizing the internal cancer-novel analysis system to integrate it into the diagnosis of CRC and tailor treatments based on genetic mutations. In the long term, these efforts could pave the way for several progress in precision succology.