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. 2023 Jan 31;4(3):208–227. doi: 10.1158/2643-3230.BCD-22-0128

Figure 7.

Figure 7. Proposed model of the molecular timing of events leading to classic Hodgkin lymphoma. Our data suggest that the initiating event in cHL can occur in a naïve B-cell prior to entry in the germinal center as evidenced by potential RAG-mediated SVs. Other early events include alterations in non–AID-mediated drivers such as B2M and GNA13 as well as deletions in PTPN1 and chromothripsis. In the GC, the premalignant cell undergoes somatic hypermutation without finalizing its maturation for unproductive BCR in most cases. Acquisition of AID-mediated events in off-target genes is not limited to early phases of cancer development, and it might be proceeded by other drivers. APOBEC mutational activity and chromosomal gains are both present in cHL and occur as intermediate/late events in cHL pathogenesis.

Proposed model of the molecular timing of events leading to classic Hodgkin lymphoma. Our data suggest that the initiating event in cHL can occur in a naïve B cell prior to entry in the germinal center as evidenced by potential RAG-mediated SVs. Other early events include alterations in non–AID-mediated drivers such as B2M and GNA13 as well as deletions in PTPN1 and chromothripsis. In the GC, the premalignant cell undergoes somatic hypermutation without finalizing its maturation for unproductive BCR in most cases. Acquisition of AID-mediated events in off-target genes is not limited to early phases of cancer development, and it might be proceeded by other drivers. APOBEC mutational activity and chromosomal gains are both present in cHL and occur as intermediate/late events in cHL pathogenesis.