2dfa5e9077672ecd77651a029303da5828159c92
CD79B.md
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| 1 | +--- |
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| 2 | +bibliography: 'morinlab.bib' |
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| 3 | +csl: 'NLM.csl' |
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| 4 | +link-citations: true |
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| 5 | +--- |
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| 1 | 6 | # CD79B |
| 2 | 7 | |
| 3 | 8 | ## Overview |
| 4 | -CD79B mutations significantly contribute to the pathogenesis of DLBCL by enhancing BCR signaling and promoting tumor survival. These mutations, especially when co-occurring with MYD88 mutations, define a unique molecular subtype.<sup>1</sup> This has clinical and therapeutic implications as it may contribute sensitivity to BTK inhibitors. In an inducible mouse model of MYD88-driven DLBCL, CD79B mutations did not accelerate lymphomagenesis but demonstrated an increased sensitivity to pharmacological BTK inhibition.<sup>2</sup> In a retrospective analysis, younger patients with MCD DLBCL that were treated with ibrutinib had significantly better outcomes.<sup>3</sup> The most common hotspot mutation in CD79B is at the tyrosine residue 196 (Y196). This and other common mutations primarily occur in the immunoreceptor tyrosine-based activation motif (ITAM) domain and prevent the negative regulatory feedback provided by Lyn kinase thereby enhancing BCR signaling. |
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| 9 | +CD79B mutations significantly contribute to the pathogenesis of DLBCL by enhancing BCR signaling and promoting tumor survival. These mutations, especially when co-occurring with MYD88 mutations, define a unique molecular subtype.<sup>1</sup> This has clinical and therapeutic implications as it may contribute sensitivity to BTK inhibitors. In an inducible mouse model of MYD88-driven DLBCL, CD79B mutations did not accelerate lymphomagenesis but demonstrated an increased sensitivity to pharmacological BTK inhibition.<sup>2</sup> In a retrospective analysis, younger patients with MCD DLBCL that were treated with ibrutinib had significantly better outcomes.<sup>3</sup> The most common hotspot mutation in CD79B is at the tyrosine residue 196 (Y196). This and other common mutations primarily occur in the immunoreceptor tyrosine-based activation motif (ITAM) domain and prevent the negative regulatory feedback provided by Lyn kinase thereby enhancing BCR signaling. |
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| 10 | + |
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| 11 | + |
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| 5 | 12 | ## History |
| 6 | 13 | ```mermaid |
| 7 | 14 | %%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% |
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| 15 | 22 | |
| 16 | 23 | |Entity|Tier|Description | |
| 17 | 24 | |:------:|:----:|--------------------------------------| |
| 18 | -| |2 |relevance in BL not firmly established| |
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| 19 | -| |1 |high-confidence DLBCL gene | |
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| 25 | +| |2 |relevance in BL not firmly established[@paneaWholeGenomeLandscape2019]| |
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| 26 | +| |1 |high-confidence DLBCL gene [@morinFrequentMutationHistonemodifying2011]| |
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| 20 | 27 | | |2 |relevance in FL not firmly established| |
| 21 | 28 | |
| 22 | 29 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |