(8,9) First, the ability to detect clonal rearrangements in post germinal center origin lymphomas is affected by somatic hypermutation
that can occur at primer binding sites (typically selected as having conserved sequences), leading to false-negative results, especially if only IGH is targeted.
, only nondominated antibodies are selected to form an active parent population A(t) (where t is the iteration counter) with the size of [N.sub.A] for undergoing cloning, crossover, and hypermutation
. This process mimics the biological immune system in which only those B-cells (antibodies) that are capable of binding with foreign antigens will undergo clonal expansion and then hypermutation
Honjo, "Class switch recombination and hypermutation
require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme," Cell, vol.
compared gene expression profile of 21 PCNSLs with purified normal GC and non-GC B-cells and showed that tumor cells had not reached the post-GC B-cell stage, but they were more closely related to memory B-cell than to GC B-cell, which suggested PCNSL derived from a late GC B-cell.[sup] These findings, combined with the presence of ongoing immunoglobulin gene somatic hypermutation
and absence of immunoglobulin class switch recombination, manifest that tumor cells of PCNSL derive from a late GC or early-post-GC origin.[sup],, However, a number of studies have discovered that the prognostic value of dividing PCNSL into GCB and ABC subgroup is not as significant as that in systemic DLBCL.
The yeast strain incorporates an inducible hypermutation
system that exclusively introduces base substitutions into a gene of interest.
pylori cagA-positive strains induces aberrant expression of activation-induced cytidine deaminase (AID), a DNA editing enzyme that physiologically introduces somatic hypermutation
in immunoglobulin variable regions in B cells.
(4) Immunoglobulin diversification based on the "somatic hypermutation
" (SHM) process, which is regulated by the MutS[alpha]-MutL[alpha] complex, in combination with two other proteins, AID (activation-induced cytidine deaminase) and Pol[mu] (DNA Polymerase "error-prone") ; in particular, MutSa deficiency is associated with neoplastic transformation of T lymphocytes 
This could be achieved through the creation of short ssDNA tracts in the S regions, paralleling somatic hypermutation
, or through RNA-DNA hybrid R-loop formation [117, 118].
In a recent study, evaluating the functional capacity of the immune system in 10 adult patients with AML using the response to seasonal influenza vaccination as a surrogate, only 2 patients generated protective titers in response to vaccination and a majority of patients had abnormal frequencies of transitional and memory B cells, with B cell repertoire showing little evidence of somatic hypermutation
. Conversely, T cell populations were similar to healthy controls, and cytotoxic T cells demonstrated antigen-specific activity after vaccination, with T-effector cells showing increased PD-1 expression with possible therapeutic implications (see specific paragraph) .
The CMS 1 subtype is characterized by hypermutation
, microsatellite instability, and strong immune activation especially .
Kulturel-Konak, "Assessing hypermutation
operators of a clonal selection algorithm for the unequal area facility layout problem," Engineering Optimization, vol.
Several strategies have been adopted to maintain diversity in dynamic optimization problems such as hypermutation
in GAs , the random immigrant scheme , prediction scheme and the memory-based methods, which are considered a special case of it , self-adaptive strategy , and multipopulation strategy [11, 24].