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Figure 1 | Molecular Medicine

Figure 1

From: Temporal Dynamics of Clonal Evolution in Chronic Lymphocytic Leukemia with Stereotyped IGHV4-34/IGKV2-30 Antigen Receptors: Longitudinal Immunogenetic Evidence

Figure 1

Restricted patterns and hotspots of ID over time. (A) Certain mutations observed within the IGHV4-34 gene of subset 4 cases. (B) Mutations within the IGKV2-30 gene of subset 4 cases. Precise targeting of ID infers strong functional constraints for preservation of critical physicochemical properties. This idea is further underscored by the observation that many UCMs (that is, mutations present in a single subcloned sequence, either at a single-case or time-point level) were present as ubiquitous mutations, CMs (that is, mutations present in more than one but less than all subcloned sequences) or UCMs in other samples or at another time point of the same sample and thus may be considered as imprints of the ID process. The substitution of isoleucine (I) with valine (V) at codon 21 (VK CDR1) together with the asparagine (N) to aspartic acid (D) change at codon 66 (VK FR3) provides an example of patterns of SHM that could perhaps be interpreted within the context of “concerted mutagenesis.” Amino acids are represented by a single-letter code. The germline amino acid is indicated in the header with the number referring to the codon position according to the IMGT unique numbering for V-DOMAIN (V-QUEST, version 2.1.2). Within the figures, the number of subcloned sequences containing a certain amino acid is indicated after the single-letter code, whereas amino acids highlighted in white exemplify the phenomenon of UCMs’ being confirmed by either a different case or another time point of the same case. A comprehensive list of amino acid changes observed in all cases analyzed is provided in Supplementary Tables S6-S8. N, number of subcloned sequences analyzed; TP time point.

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