BCR.pdf
... ...
Binary files a/BCR.pdf and /dev/null differ
HNRNPH1.md
... ...
@@ -1,6 +1,6 @@
1 1
# HNRNPH1
2 2
## Overview
3
-Mutations in HNRNPH1 are enriched at splicing signals in exon 4. These result in deregulated splicing and increased expression of the hnRNP H1 protein. This overexpression is linked to enhanced cell proliferation and survival, contributing to the aggressive nature of MCL. <sup>1,2</sup> Although initially characterized in MCL, the same pattern of mutations appears in a small number of DLBCLs.
3
+Non-coding mutations, including synonymous and intronic mutations, are enriched at splicing signals in exon 4 of HNRNPH1. These result in deregulated splicing and increased expression of the hnRNP H1 protein. This overexpression is linked to enhanced cell proliferation and survival, contributing to the aggressive nature of MCL. <sup>1,2</sup> Although initially characterized in MCL, the same pattern of mutations appears in a small number of DLBCLs.
4 4
5 5
## Relevance tier by entity
6 6
... ...
@@ -27,10 +27,6 @@ Mutations in HNRNPH1 are enriched at splicing signals in exon 4. These result in
27 27
|DLBCL |No |No |2.337 |10.139 |
28 28
|FL |No |No |0.000 | 0.000 |
29 29
30
-
31
-> [!NOTE]
32
-> First described in MCL in 2020 by [Pararajalingam P](https://pubmed.ncbi.nlm.nih.gov/32160292)
33
-
34 30
## HNRNPH1 Hotspots
35 31
36 32
| Chromosome |Coordinate (hg19) | ref>alt | HGVSp |
... ...
@@ -45,8 +41,12 @@ View all variants in GenomePaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/H
45 41
46 42
![image](images/proteinpaint/HNRNPH1.svg)
47 43
44
+## HNRNPH1 Expression
45
+![image](images/gene_expression/HNRNPH1_by_pathology.svg)
46
+
47
+
48 48
## References
49 49
1. *Pararajalingam, P., Coyle, K., Arthur, S., Thomas, N., Alcaide, M., Meissner, B., Boyle, M., Qureshi, Q., Grande, B., Rushton, C., Slack, G., Mungall, A., Tam, C., Agarwal, R., Dawson, S., Lenz, G., Balasubramanian, S., Gascoyne, R., Steidl, C., Connors, J., Villa, D., Audas, T., Marra, M., Johnson, N., Scott, D., & Morin, R. (2020). Coding and non-coding drivers of mantle cell lymphoma identified through exome and genome sequencing.. Blood. https://doi.org/10.1182/blood.2019002385.*
50 50
2. *Coyle, K., Qureshi, Q., Pararajalingam, P., Thomas, N., Audas, T., & Morin, R. (2020). Perturbations in HNRNPH1 Splicing and Abundance Affect Global Splicing and Proliferation in Mantle Cell Lymphoma. Blood, 136, 23-24. https://doi.org/10.1182/BLOOD-2020-141389.*
51
-## HNRNPH1 Expression
52
-![image](images/gene_expression/HNRNPH1_by_pathology.svg)
51
+
52
+<!-- NONCODING -->
HNRNPU.md
... ...
@@ -1,61 +0,0 @@
1
-# HNRNPU
2
-## Overview
3
-HNRNPU 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 HNRNPU are haploinsufficient and significantly alter the transcriptome of MYC-driven lymphomas. These mutations were found in a notable percentage of high-grade B-cell lymphomas with double-hit BCL2 translocations (HGBL-DH-BCL2) and Burkitt lymphoma (BL).<sup>1</sup>
4
-
5
-## Relevance tier by entity
6
-
7
-|Entity|Tier|Description |
8
-|:------:|:----:|--------------------------|
9
-|BL |1-a | aSHM target and high-confidence BL gene |
10
-|DLBCL |1-a | aSHM target and high-confidence DLBCL gene|
11
-
12
-## Mutation incidence in large patient cohorts (GAMBL reanalysis)
13
-
14
-|Entity|source |frequency (%)|
15
-|:------:|:---------------------:|:-------------:|
16
-|BL |GAMBL genomes+capture|5.77 |
17
-|BL |Thomas cohort |6.40 |
18
-|BL |Panea cohort |8.90 |
19
-|DLBCL |GAMBL genomes |2.49 |
20
-|DLBCL |Schmitz cohort |3.40 |
21
-|DLBCL |Reddy cohort |2.40 |
22
-|DLBCL |Chapuy cohort |3.42 |
23
-
24
-## Mutation pattern and selective pressure estimates
25
-
26
-|Entity|aSHM|Significant selection|dN/dS (missense)|dN/dS (nonsense)|
27
-|:------:|:----:|:---------------------:|:----------------:|:----------------:|
28
-|BL |Yes |Yes |1.081 |27.052 |
29
-|DLBCL |Yes |No |1.712 | 0.000 |
30
-|FL |Yes |No |4.865 |31.056 |
31
-
32
-## aSHM regions
33
-
34
-|chr_name|hg19_start|hg19_end |region |regulatory_comment|
35
-|:--------:|:----------:|:---------:|:-------------------------------------------------------------------------------------------:|:------------------:|
36
-|chr1 |245023502 |245029083|[TSS](https://genome.ucsc.edu/s/rdmorin/GAMBL%20hg19?position=chr1%3A245023502%2D245029083)|NA |
37
-
38
-> [!NOTE]
39
-> First described in BL in 2019 by [Panea RI](https://pubmed.ncbi.nlm.nih.gov/31558468)
40
-
41
-
42
- ## HNRNPU Hotspots
43
-
44
-| Chromosome |Coordinate (hg19) | ref>alt | HGVSp |
45
- | :---:| :---: | :--: | :---: |
46
-| chr1 | 245027102 | G>A | Q170* |
47
-| chr1 | 245027099 | G>C | Q171E |
48
-| chr1 | 245027099 | G>A | Q171* |
49
-
50
-View coding variants in ProteinPaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/HNRNPU_protein.html) or [hg38](https://morinlab.github.io/LLMPP/GAMBL/HNRNPU_protein_hg38.html)
51
-
52
-![image](images/proteinpaint/HNRNPU_NM_031844.svg)
53
-
54
-View all variants in GenomePaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/HNRNPU.html) or [hg38](https://morinlab.github.io/LLMPP/GAMBL/HNRNPU_hg38.html)
55
-
56
-![image](images/proteinpaint/HNRNPU.svg)
57
-
58
-## References
59
-1. *Qureshi, Q., Coyle, K., Thomas, N., Collinge, B., Dreval, K., Hilton, L., Wong, J., Scott, D., Audas, T., & Morin, R. (2023). Hnrnpu mutations Are Haploinsufficient and Alter the Transcriptome of MYC-Driven Lymphomas. Blood. https://doi.org/10.1182/blood-2023-190409.*
60
-## HNRNPU Expression
61
-![image](images/gene_expression/HNRNPU_by_pathology.svg)
NFKBIZ.md
... ...
@@ -40,8 +40,11 @@ View coding variants in ProteinPaint [hg19](https://morinlab.github.io/LLMPP/GAM
40 40
View all variants in GenomePaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/NFKBIZ.html) or [hg38](https://morinlab.github.io/LLMPP/GAMBL/NFKBIZ_hg38.html)
41 41
42 42
![image](images/proteinpaint/NFKBIZ.svg)
43
+
43 44
## NFKBIZ Expression
44 45
![image](images/gene_expression/NFKBIZ_by_pathology.svg)
45 46
46 47
## References
47 48
1. *Arthur SE, Jiang A, Grande BM, Alcaide M, Cojocaru R, Rushton CK, Mottok A, Hilton LK, Lat PK, Zhao EY, Culibrk L, Ennishi D, Jessa S, Chong L, Thomas N, Pararajalingam P, Meissner B, Boyle M, Davidson J, Bushell KR, Lai D, Farinha P, Slack GW, Morin GB, Shah S, Sen D, Jones SJM, Mungall AJ, Gascoyne RD, Audas TE, Unrau P, Marra MA, Connors JM, Steidl C, Scott DW, Morin RD. Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma. Nat Commun. 2018 Oct 1;9(1):4001. doi: 10.1038/s41467-018-06354-3. PMID: 30275490; PMCID: PMC6167379.*
49
+
50
+<!-- NONCODING -->
NFKBIZ.pdf
... ...
Binary files a/NFKBIZ.pdf and /dev/null differ