b'IGH Somatic HypermutationClinical InformationLymphoid cells are different from the other somatic cellsImmunoglobulin variable heavy chain gene hypermutation in the body as during development, the antigen receptorstatus provides important prognostic information for genes in these cells undergo somatic gene rearrangement. 1 patients with chronic lymphocytic leukemia (CLL) and During B-cell development, genes encoding the humansmall lymphocytic lymphoma (SLL). The presence of IGH immunoglobulin heavy chain (IGH) proteins are assembledSHM is defined as greater or equal to 2% difference from from multiple polymorphic gene segments that undergothe germline VH gene sequence, whereas less than 2% rearrangements and selection, generating V H -D H -J H difference is considered evidence of no SHM. The status combinations that are unique in both length and sequenceof SHM for clone(s) has clinical relevance, as there is a for each cell. 2-3An additional level of diversity is generatedclear distinction in the median survival of patients with and by point mutations in the variable regions, also known aswithout SHM. Hypermutation of the IGH variable region somatic hypermutations (SHM).is strongly predictive of a good prognosis, while lack of Leukemias and lymphomas originate from the malignantmutation predicts a poor prognosis. 4In addition, this assay transformation of individual lymphoid cells, which meansidentifies clonal rearrangements involving the V3-21 gene, that all leukemias and lymphomas generally share onewhich has been associated with a poor prognosis in CLL independent of SHM status. This assay has been shownor more cell-specific or clonal antigen receptor geneto further stratify CLL patients. 5rearrangements. Therefore, tests that detect IGH clonal rearrangements can be useful in the study of B-cell malignancies. References:1.Tonegawa S (1983). Somatic Generation of Antibody Diversity. Nature 302:575-581.2.Trainor KJ et al. (1990). Monoclonality in B-lymphoproliferative disorders detected at the DNA level. Blood 75:2220-2222.3.JE Miller et al., Molecular Genetic Pathology (2013, 2nd ed.) Springer Science & Business Media 302.2.7.13 and 30.2.7.18. 4.P. Ghia, et al. (2007). ERIC recommendations on IGHV gene mutational status in chronic lymphocytic leukemia. Leukemia 21:1-3. 5.Stamatopoulos, B et al. (2017). Targeted deep sequencing reveals clinically relevant subclonal IgHV rearrangements inchronic lymphocytic leukemia. Leukemia 31(4):837-845.26'