2365d234c648fd54e7fc58a6b6c49f43d9f3f8d7
BTG2.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 | # BTG2 |
| 2 | 7 | |
| 3 | 8 | ## Overview |
| 4 | 9 | BTG2 is one of [a number of genes](https://github.com/morinlab/LLMPP/wiki/ashm) affected by aberrant somatic hypermutation in B-cell lymphomas, which complicates the interpretation of mutations at this locus. Mutations in the BTG2 gene have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL), contributing to the development and progression of the disease. These mutations are a feature of the MCD genetic subgroup of DLBCL.<sup>1</sup> The biological function of BTG2 mutations and their role in lymphomagenesis remains poorly understood. A potential prognostic association with BTG2 mutations in primary testicular DLBCL has been reported but this has not yet been reproduced.<sup>2</sup> |
| 10 | + |
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| 5 | 11 | ## History |
| 6 | 12 | |
| 7 | 13 | ```mermaid |
| ... | ... | @@ -16,9 +22,9 @@ timeline |
| 16 | 22 | |
| 17 | 23 | |Entity|Tier|Description | |
| 18 | 24 | |:------:|:----:|--------------------------------------| |
| 19 | -| |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous | |
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| 20 | -| |1-a | aSHM target and high-confidence DLBCL gene | |
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| 21 | -| |1-a | aSHM target and high-confidence FL gene | |
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| 25 | +| |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@loveGeneticLandscapeMutations2012]| |
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| 26 | +| |1-a | aSHM target and high-confidence DLBCL gene [@morinFrequentMutationHistonemodifying2011]| |
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| 27 | +| |1-a | aSHM target and high-confidence FL gene [@morinFrequentMutationHistonemodifying2011]| |
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| 22 | 28 | |
| 23 | 29 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 24 | 30 |
BTK.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 | # BTK |
| 2 | 7 | One study reported BTK mutations in approximately 7% of FL and 11% of transformed FL cases.<sup>1</sup> Another showed these mutations were more common, and typically co-occur in tumours with BCL2 translocations. Despite the known role of certain BTK mutations in acquired resistance to BTK inhibitors, these mutations were found in BTK inhibitor-naïve patients.<sup>2</sup> These mutations often occur in treatment-naive patients and lead to inactivation of the BTK protein through destabilization or by altering key residues involved in enzymatic activity.<sup>1</sup> The mutation pattern in DLBCL and FL implies the preferential accumulation of *inactivating mutations*. No notable hot spots have been described in this gene in the context of the cancers listed below. |
| 8 | + |
|
| 3 | 9 | ## History |
| 4 | 10 | ```mermaid |
| 5 | 11 | %%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% |
| ... | ... | @@ -13,8 +19,8 @@ timeline |
| 13 | 19 | |
| 14 | 20 | |Entity|Tier|Description | |
| 15 | 21 | |:------:|:----:|--------------------------| |
| 16 | -| |1 |high-confidence DLBCL gene| |
|
| 17 | -| |1 |high-confidence FL gene | |
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| 22 | +| |1 |high-confidence DLBCL gene[@albuquerqueEnhancingKnowledgeDiscovery2017a]| |
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| 23 | +| |1 |high-confidence FL gene [@krysiakRecurrentSomaticMutations2017b]| |
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| 18 | 24 | |
| 19 | 25 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 20 | 26 |
CD58.md
| ... | ... | @@ -1,8 +1,14 @@ |
| 1 | +--- |
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| 2 | +bibliography: 'morinlab.bib' |
|
| 3 | +csl: 'NLM.csl' |
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| 4 | +link-citations: true |
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| 5 | +--- |
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| 1 | 6 | # CD58 |
| 2 | 7 | |
| 3 | 8 | ## Overview |
| 4 | 9 | |
| 5 | 10 | CD58, also known as lymphocyte function-associated antigen 3 (LFA-3), is crucial for immune recognition, facilitating interactions between tumor cells and cytotoxic T cells and natural killer (NK) cells. In DLBCL, mutations prevent the expression of CD58 on the cell surface, impairing the ability of T and NK cells to recognize and attack the tumor cells. This is often accompanied by mutations in the β2-Microglobulin gene, which further aids in immune evasion.<sup>1</sup> |
| 11 | + |
|
| 6 | 12 | ## History |
| 7 | 13 | ```mermaid |
| 8 | 14 | %%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% |
| ... | ... | @@ -16,8 +22,8 @@ timeline |
| 16 | 22 | |
| 17 | 23 | |Entity|Tier|Description | |
| 18 | 24 | |:------:|:----:|--------------------------------------| |
| 19 | -||1|high-confidence PMBL/cHL/GZL gene| |
|
| 20 | -| |1 |high-confidence DLBCL gene | |
|
| 25 | +||1|high-confidence PMBL/cHL/GZL gene[@schneiderAlterationsCD58Gene2015a]| |
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| 26 | +| |1 |high-confidence DLBCL gene [@morinFrequentMutationHistonemodifying2011]| |
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| 21 | 27 | |
| 22 | 28 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 23 | 29 |
CD70.md
| ... | ... | @@ -1,7 +1,14 @@ |
| 1 | +--- |
|
| 2 | +bibliography: 'morinlab.bib' |
|
| 3 | +csl: 'NLM.csl' |
|
| 4 | +link-citations: true |
|
| 5 | +--- |
|
| 1 | 6 | # CD70 |
| 2 | 7 | |
| 3 | 8 | ## Overview |
| 4 | -CD70 is a costimulatory molecule expressed on some activated lymphocytes and has a role in T-cell-mediated immune responses.<sup>1</sup> CD70 aberrations are relatively common in DLBCL and appear more frequent in certain DLBCL patient populations. For instance, in a Chinese DLBCL cohort, 24% of cases exhibited CD70 genetic changes, compared to 10.8% in a Swedish cohort.<sup>1</sup> CD70 mutations are associated with the BN2 genetic subtype of DLBCL.<sup>2</sup> The mutation pattern in CD70 is consistent with the preferential accumulation of *inactivating mutations*. Loss of CD70 protein expression has been described.<sup>1</sup> Genetic perturbation limits the development of an effective CD8+ T-cell immune response in Bcl6-driven DLBCL. In mouse models, CD70 loss promoted lymphomagenesis, consistent with its role as a tumor suppressor gene in B-cell lymphomas.<sup>1,3</sup> |
|
| 9 | +CD70 is a costimulatory molecule expressed on some activated lymphocytes and has a role in T-cell-mediated immune responses. CD70 aberrations are relatively common in DLBCL and appear more frequent in certain DLBCL patient populations. For instance, in a Chinese DLBCL cohort, 24% of cases exhibited CD70 genetic changes, compared to 10.8% in a Swedish cohort.<sup>1</sup> CD70 mutations are associated with the BN2 genetic subtype of DLBCL.<sup>2</sup> The mutation pattern in CD70 is consistent with the preferential accumulation of *inactivating mutations*. Loss of CD70 protein expression has been described.<sup>1</sup> Genetic perturbation limits the development of an effective CD8+ T-cell immune response in Bcl6-driven DLBCL. |
|
| 10 | +In mouse models, CD70 loss promoted lymphomagenesis, consistent with its role as a tumor suppressor gene in B-cell lymphomas. |
|
| 11 | + |
|
| 5 | 12 | ## History |
| 6 | 13 | ```mermaid |
| 7 | 14 | %%{init: { 'logLevel': 'debug', 'theme': 'dark' } }%% |
| ... | ... | @@ -15,8 +22,8 @@ timeline |
| 15 | 22 | |
| 16 | 23 | |Entity|Tier|Description | |
| 17 | 24 | |:------:|:----:|--------------------------------------| |
| 18 | -| |1 |high-confidence DLBCL gene | |
|
| 19 | -| |2 |relevance in FL not firmly established| |
|
| 25 | +| |1 |high-confidence DLBCL gene [@morinFrequentMutationHistonemodifying2011]| |
|
| 26 | +| |2 |relevance in FL not firmly established[@russler-germainMutationsAssociatedProgression2023b]| |
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| 20 | 27 | |
| 21 | 28 | ## Mutation incidence in large patient cohorts (GAMBL reanalysis) |
| 22 | 29 | |
| ... | ... | @@ -58,12 +65,12 @@ View all variants in GenomePaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/C |
| 58 | 65 | |
| 59 | 66 |  |
| 60 | 67 | |
| 61 | -# References |
|
| 62 | -1. *Nie M, Ren W, Ye X, Berglund M, Wang X, Fjordén K, Du L, Giannoula Y, Lei D, Su W, Li W, Liu D, Linderoth J, Jiang C, Bao H, Jiang W, Huang H, Hou Y, Zhu S, Enblad G, Jerkeman M, Wu K, Zhang H, Amini RM, Li ZM, Pan-Hammarström Q. The dual role of CD70 in B-cell lymphomagenesis. Clin Transl Med. 2022 Dec;12(12):e1118. doi: 10.1002/ctm2.1118. PMID: 36471481; PMCID: PMC9722974.* |
|
| 63 | -2. *Wright GW, Huang DW, Phelan JD, Coulibaly ZA, Roulland S, Young RM, Wang JQ, Schmitz R, Morin RD, Tang J, Jiang A, Bagaev A, Plotnikova O, Kotlov N, Johnson CA, Wilson WH, Scott DW, Staudt LM. A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications. Cancer Cell. 2020 Apr 13;37(4):551-568.e14. doi: 10.1016/j.ccell.2020.03.015. PMID: 32289277; PMCID: PMC8459709.* |
|
| 64 | -3. *Mandato, E., Calabretta, E., Bai, G., Song, L., Sun, Y., Shanmugam, V., Paczkowska, J., Choi, I., Redd, R., Tang, M., Lawton, L., Neuberg, D., Rodig, S., Michor, F., Zhang, B., & Shipp, M. (2022). Abstract A38: Cd70 genetic perturbation limits the development of an effective CD8+ T-cell immune response to Bcl6-driven diffuse large B-cell lymphoma. Blood Cancer Discovery. https://doi.org/10.1158/2643-3249.lymphoma22-a38.* |
|
| 65 | 68 | ## CD70 Expression |
| 66 | 69 |  |
| 67 | 70 | <!-- ORIGIN: morinFrequentMutationHistonemodifying2011 --> |
| 68 | 71 | <!-- DLBCL: morinFrequentMutationHistonemodifying2011 --> |
| 69 | 72 | <!-- FL: russler-germainMutationsAssociatedProgression2023b --> |
| 73 | + |
|
| 74 | +## References |
|
| 75 | + |
|
| 76 | + |