Review of genetics and epigenetics of NHL cancer

Lymphomas are solid tumors of the immune system. Hodgkin's lymphoma accounts for about ۱۰% of all lymphomas, and the remaining ۹۰% are referred to as non-Hodgkin lymphoma (NHL). NHL is a heterogeneous group of hematological malignancies characterized by genetic alterations that contribute to their development and progression Understanding the genetic basis of NHL is crucial for identifying risk factors, improving diagnostic methods, and developing targeted therapies. Familial predisposition to NHL has been observed, with first-degree relatives of patients showing increased risks of developing the disease. For instance, first-degree relatives of NHL patients have about a ۱.۷-fold elevated risk. However, while familial forms exist, most cases are sporadic, and the hereditary patterns do not follow simple Mendelian inheritance. Instead, there appears to be a genetic susceptibility that may involve multiple genes and environmental interactions. Most genetic alterations in NHL are somatic mutations, meaning they arise during an individual's lifetime rather than being inherited. Key genes implicated in these mutations include CASP۱۰, ATM, BRAF, EZH۲, and CREBBP among others. Notably, the PRF۱ gene is an exception, associated with an autosomal recessive form of non-Hodgkin lymphoma in specific cases. there are two types of NHL, B-cell NHL(accounting for about ۸۵-۹۰% of all non-Hodgkin lymphoma cases) and T-cell NHL.NHL encompasses various subtypes, Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide, representing approximately ۳۰-۴۰% of all cases in different geographic regions each of these subtypes has different genetic characteristics: DLBCL: Common alterations include translocations involving the MYC oncogene and the BCL۲ gene. Follicular Lymphoma (FL): Characterized by the t(۱۴;۱۸) translocation involving the BCL۲ gene, which prevents normal cell death and promotes lymphocyte survival. Burkitt Lymphoma (BL): Often associated with MYC translocations (e.g. t(۸;۱۴)), leading to uncontrolled cell proliferation. Mantle Cell Lymphoma: Frequently involves the t(۱۱;۱۴) translocation affecting the BCL۱ gene. Epigenetics also plays a role in pathogenesis DNA methylation is a prominent epigenetic modification in NHL, particularly involving the hypermethylation of promoter regions of tumor suppressor genes. Commonly affected genes include p۱۵INK۴b, p۱۶INK۴a, MGMT, and RARβ۲. Histone modifications also significantly impact the NHL. Mutations in genes encoding histone-modifying enzymes, such as CREBBP and KMT۲D, are frequently observed in various NHL subtypes. For example, loss-of-function mutations in KMT۲D occur in approximately ۹۰% of follicular lymphoma (FL) cases and about ۳۰% of diffuse large B-cell lymphoma (DLBCL) cases The genetics and epigenetics of non-Hodgkin lymphoma are complex and multifaceted. While familial predisposition indicates a hereditary component, most genetic changes are acquired during life. Understanding the molecular genetics of NHL will be essential for developing more effective diagnostic tools and treatment strategies tailored to individual patient profiles.

کلیدواژه ها:

non-Hodgkin lymphoma ، DLBCL ، Follicular Lymphoma ، Burkitt Lymphoma ، Mantle Cell Lymphoma