fix referencing

-| |2 |relevance in BL not firmly established[@loveGeneticLandscapeMutations2012]|

-| |2-a | aSHM target; Although recurrent, the relevance of mutations in BL is tenuous [@loveGeneticLandscapeMutations2012]|

-### *196 total*

-|[HNRNPD](HNRNPD)|2|||

-| |2 |relevance in DLBCL not firmly established|

-1. Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ, Roulland S, Kasbekar M, Young RM, Shaffer AL, Hodson DJ, Xiao W, Yu X, Yang Y, Zhao H, Xu W, Liu X, Zhou B, Du W, Chan WC, Jaffe ES, Gascoyne RD, Connors JM, Campo E, Lopez-Guillermo A, Rosenwald A, Ott G, Delabie J, Rimsza LM, Tay Kuang Wei K, Zelenetz AD, Leonard JP, Bartlett NL, Tran B, Shetty J, Zhao Y, Soppet DR, Pittaluga S, Wilson WH, Staudt LM. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. N Engl J Med. 2018 Apr 12;378(15):1396–1407. PMCID: PMC6010183

-| |1 |high-confidence DLBCL gene |

-1. Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, Wells VA, Grunn A, Messina M, Elliot O, Chan J, Bhagat G, Chadburn A, Gaidano G, Mullighan CG, Rabadan R, Dalla-Favera R. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011 Jul 31;43(9):830–837. PMCID: PMC3297422

-| |1-a | aSHM target and high-confidence DLBCL gene|

-1. *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.*

-1. Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, Richards KL, Dunphy CH, Choi WWL, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers CR, Naresh KN, Evens AM, Chadburn A, Gordon LI, Czader MB, Gill JI, Hsi ED, Greenough A, Moffitt AB, McKinney M, Banerjee A, Grubor V, Levy S, Dunson DB, Dave SS. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012 Dec;44(12):1321–1325. PMCID: PMC3674561

-| |2 |relevance in MCL not firmly established|

-1. Zhang J, Jima D, Moffitt AB, Liu Q, Czader M, Hsi ED, Fedoriw Y, Dunphy CH, Richards KL, Gill JI, Sun Z, Love C, Scotland P, Lock E, Levy S, Hsu DS, Dunson D, Dave SS. The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells. Blood. 2014 May 8;123(19):2988–2996.

-| |2 |relevance in FL not firmly established|

-1. Russler-Germain DA, Krysiak K, Ramirez CA, Mosior M, Watkins MP, Gomez F, Skidmore ZL, Trani L, Gao F, Geyer S, Cashen A, Mehta-Shah N, Kahl B, Bartlett N, Alderuccio J, Lossos I, Ondrejka S, Hsi E, Martin P, Leonard J, Griffith M, Griffith O, Fehniger T. Mutations associated with progression in follicular lymphoma predict inferior outcomes at diagnosis: Alliance A151303. Blood Advances. 2023;7:5524–5539.

-| |2 |relevance in DLBCL not firmly established|

-1. Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ, Roulland S, Kasbekar M, Young RM, Shaffer AL, Hodson DJ, Xiao W, Yu X, Yang Y, Zhao H, Xu W, Liu X, Zhou B, Du W, Chan WC, Jaffe ES, Gascoyne RD, Connors JM, Campo E, Lopez-Guillermo A, Rosenwald A, Ott G, Delabie J, Rimsza LM, Tay Kuang Wei K, Zelenetz AD, Leonard JP, Bartlett NL, Tran B, Shetty J, Zhao Y, Soppet DR, Pittaluga S, Wilson WH, Staudt LM. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. N Engl J Med. 2018 Apr 12;378(15):1396–1407. PMCID: PMC6010183

-| |2 |relevance in BL not firmly established|

-1. Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, Wright G, Shaffer AL, Hodson DJ, Buras E, Liu X, Powell J, Yang Y, Xu W, Zhao H, Kohlhammer H, Rosenwald A, Kluin P, Müller-Hermelink HK, Ott G, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Ogwang MD, Reynolds SJ, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pittaluga S, Wilson W, Waldmann TA, Rowe M, Mbulaiteye SM, Rickinson AB, Staudt LM. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012 Oct 4;490(7418):116–120. PMCID: PMC3609867

-| |2 |relevance in DLBCL not firmly established|

-1. Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC, Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A, Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL, Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors JM, Gascoyne RD, Marra MA. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013 Aug 15;122(7):1256–1265. PMCID: PMC3744992

-| |2 |relevance in MCL not firmly established|

-1. Zhang J, Jima D, Moffitt AB, Liu Q, Czader M, Hsi ED, Fedoriw Y, Dunphy CH, Richards KL, Gill JI, Sun Z, Love C, Scotland P, Lock E, Levy S, Hsu DS, Dunson D, Dave SS. The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells. Blood. 2014 May 8;123(19):2988–2996.

- 2019-09-26 : [Panea](papers/paneaWholeGenomeLandscape2019) : BL

-1. Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, Monti S, Vaisitti T, Arruga F, Famà R, Ciardullo C, Greco M, Cresta S, Piranda D, Holmes A, Fabbri G, Messina M, Rinaldi A, Wang J, Agostinelli C, Piccaluga PP, Lucioni M, Tabbò F, Serra R, Franceschetti S, Deambrogi C, Daniele G, Gattei V, Marasca R, Facchetti F, Arcaini L, Inghirami G, Bertoni F, Pileri SA, Deaglio S, Foà R, Dalla-Favera R, Pasqualucci L, Rabadan R, Gaidano G. The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. J Exp Med. 2012 Aug 27;209(9):1537–1551. PMCID: PMC3428941

-2. Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, Scott DW, Ding J, Roth A, Chiu R, Corbett RD, Chan FC, Mendez-Lago M, Trinh DL, Bolger-Munro M, Taylor G, Hadj Khodabakhshi A, Ben-Neriah S, Pon J, Meissner B, Woolcock B, Farnoud N, Rogic S, Lim EL, Johnson NA, Shah S, Jones S, Steidl C, Holt R, Birol I, Moore R, Connors JM, Gascoyne RD, Marra MA. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013 Aug 15;122(7):1256–1265. PMCID: PMC3744992

-3. Krysiak K, Gomez F, White BS, Matlock M, Miller CA, Trani L, Fronick CC, Fulton RS, Kreisel F, Cashen AF, Carson KR, Berrien-Elliott MM, Bartlett NL, Griffith M, Griffith OL, Fehniger TA. Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma. Blood. 2017 Jan 26;129(4):473–483. PMCID: PMC5270390

-4. Panea R, Love C, Shingleton JR, Reddy A, Bailey J, Moormann A, Otieno J, Ong’echa J, Oduor C, Schroêder K, Masalu N, Chao N, Agajanian M, Major M, Fedoriw Y, Richards K, Rymkiewicz G, Miles R, Alobeid B, Bhagat G, Flowers C, Ondrejka S, Hsi E, Choi W, Au-Yeung R, Hartmann W, Lenz G, Meyerson H, Lin YY, Zhuang Y, Luftig M, Waldrop A, Dave T, Thakkar D, Sahay H, Li G, Palus B, Seshadri V, Kim S, Gascoyne R, Levy S, Mukhopadhyay M, Dunson D, Dave S. The whole genome landscape of Burkitt lymphoma subtypes. Blood. 2019;

-Mutations in the HLA-B gene have been associated with a loss of cell surface expression of HLA class I molecules, which are essential for presenting tumor antigens to cytotoxic T cells. This is a common mechanism of immune escape in DLBCL. Deletions of this gene are more commonly reported than HLA-B mutations.¹ The mutation pattern in DLBCL implies the preferential accumulation of *inactivating mutations*. Different analytical strategies relating to the mapping of sequencing data and subtracting common germline variants can complicate the detection of mutations in this and other HLA genes. Likely owing to this, the rate of mutations is highly variable across studies and the true mutation rate has not been firmly established.

-||2|relevance in PMBL/cHL/GZL not firmly established|

-| |1 |high-confidence DLBCL gene |

-1. *Riemersma, S., Jordanova, E., Schop, R., Philippo, K., Looijenga, L., Schuuring, E., & Kluin, P. (2000). Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites.. Blood, 96 10, 3569-77 . https://doi.org/10.1182/BLOOD.V96.10.3569.*

-Mutations in the HLA-B gene have been associated with a loss of cell surface expression of HLA class I molecules, which are essential for presenting tumor antigens to cytotoxic T cells. This is a common mechanism of immune escape in DLBCL. Deletions of this gene are more commonly reported than HLA-B mutations.¹ The mutation pattern in DLBCL implies the preferential accumulation of *inactivating mutations*. Different analytical strategies relating to the mapping of sequencing data and subtracting common germline variants can complicate the detection of mutations in this and other HLA genes. Likely owing to this, the rate of mutations is highly variable across studies and the true mutation rate has not been firmly established.

-||1|high-confidence PMBL/cHL/GZL gene|

-| |1 |high-confidence DLBCL gene |

-1. *Riemersma, S., Jordanova, E., Schop, R., Philippo, K., Looijenga, L., Schuuring, E., & Kluin, P. (2000). Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites.. Blood, 96 10, 3569-77 . https://doi.org/10.1182/BLOOD.V96.10.3569.*

-Mutations in the HLA-C gene have been associated with a loss of cell surface expression of HLA class I molecules, which are essential for presenting tumor antigens to cytotoxic T cells. This is a common mechanism of immune escape in DLBCL. Deletions of this gene are more commonly reported than HLA-C mutations.¹ The mutation pattern in DLBCL implies the preferential accumulation of *inactivating mutations*. Different analytical strategies relating to the mapping of sequencing data and subtracting common germline variants can complicate the detection of mutations in this and other HLA genes. Likely owing to this, the rate of mutations is highly variable across studies and the true mutation rate has not been firmly established.

-||2|relevance in PMBL/cHL/GZL not firmly established|

-1. Gomez F, Fisk B, McMichael JF, Mosior M, Foltz JA, Skidmore ZL, Duncavage EJ, Miller CA, Abel H, Li YS, Russler-Germain DA, Krysiak K, Watkins MP, Ramirez CA, Schmidt A, Martins Rodrigues F, Trani L, Khanna A, Wagner JA, Fulton RS, Fronick CC, O’Laughlin MD, Schappe T, Cashen AF, Mehta-Shah N, Kahl BS, Walker J, Bartlett NL, Griffith M, Fehniger TA, Griffith OL. Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma. Cancer Res Commun. 2023 Nov 15;3(11):2312–2330. PMCID: PMC10648575

-Mutations in this gene are relatively rare in DLBCL overall. *Without further support, this gene may be migrated to Tier 2.*

-| |1 |high-confidence DLBCL gene|

-| |1 |high-confidence DLBCL gene|

-1. Hübschmann D, Kleinheinz K, Wagener R, Bernhart SH, López C, Toprak UH, Sungalee S, Ishaque N, Kretzmer H, Kreuz M, Waszak SM, Paramasivam N, Ammerpohl O, Aukema SM, Beekman R, Bergmann AK, Bieg M, Binder H, Borkhardt A, Borst C, Brors B, Bruns P, Carrillo de Santa Pau E, Claviez A, Doose G, Haake A, Karsch D, Haas S, Hansmann ML, Hoell JI, Hovestadt V, Huang B, Hummel M, Jäger-Schmidt C, Kerssemakers JNA, Korbel JO, Kube D, Lawerenz C, Lenze D, Martens JHA, Ott G, Radlwimmer B, Reisinger E, Richter J, Rico D, Rosenstiel P, Rosenwald A, Schillhabel M, Stilgenbauer S, Stadler PF, Martín-Subero JI, Szczepanowski M, Warsow G, Weniger MA, Zapatka M, Valencia A, Stunnenberg HG, Lichter P, Möller P, Loeffler M, Eils R, Klapper W, Hoffmann S, Trümper L, ICGC MMML-Seq consortium, ICGC DE-Mining consortium, BLUEPRINT consortium, Küppers R, Schlesner M, Siebert R. Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas. Leukemia. 2021 Jul;35(7):2002–2016. PMCID: PMC8257491

-| |2 |relevance in BL not firmly established|

-1. Burkhardt B, Michgehl U, Rohde J, Erdmann T, Berning P, Reutter K, Rohde M, Borkhardt A, Burmeister T, Dave S, Tzankov A, Dugas M, Sandmann S, Fend F, Finger J, Mueller S, Gökbuget N, Haferlach T, Kern W, Hartmann W, Klapper W, Oschlies I, Richter J, Kontny U, Lutz M, Maecker-Kolhoff B, Ott G, Rosenwald A, Siebert R, von Stackelberg A, Strahm B, Woessmann W, Zimmermann M, Zapukhlyak M, Grau M, Lenz G. Clinical relevance of molecular characteristics in Burkitt lymphoma differs according to age. Nat Commun. 2022 Jul 6;13(1):3881. PMCID: PMC9259584

-| |2 |relevance in DLBCL not firmly established|

-1. Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, Wells VA, Grunn A, Messina M, Elliot O, Chan J, Bhagat G, Chadburn A, Gaidano G, Mullighan CG, Rabadan R, Dalla-Favera R. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011 Jul 31;43(9):830–837. PMCID: PMC3297422

-# HNRNPD

-

-## Overview

-hnRNPs are a family of RNA-binding proteins that play crucial roles in RNA processing, including splicing, stability, transport, and translation. They are involved in the regulation of gene expression at multiple levels. HNRNPD mutations are rare in DLBCL. The mutation pattern in DLBCL and FL implies the preferential accumulation of *inactivating mutations*.

-

-## Relevance tier by entity

-

-|Entity|Tier|Description |

-|:------:|:----:|--------------------------------------|

-| |2 |relevance in DLBCL not firmly established|

-| |2 |relevance in FL not firmly established|

-

-## Mutation incidence in large patient cohorts (GAMBL reanalysis)

-

-|Entity|source |frequency (%)|

-|:------:|:--------------:|:-------------:|

-|DLBCL |GAMBL genomes |2.10 |

-|DLBCL |Schmitz cohort|2.13 |

-|DLBCL |Reddy cohort |1.80 |

-|DLBCL |Chapuy cohort |0.85 |

-|FL |GAMBL genomes | NA |

-

-## Mutation pattern and selective pressure estimates

-

-|Entity|aSHM|Significant selection|dN/dS (missense)|dN/dS (nonsense)|

-|:------:|:----:|:---------------------:|:----------------:|:----------------:|

-|BL |No |No |0.000 |19.81 |

-|DLBCL |No |No |1.554 | 0.00 |

-|FL |No |No |0.000 | 0.00 |

-

-

-

-View coding variants in ProteinPaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/HNRNPD_protein.html) or [hg38](https://morinlab.github.io/LLMPP/GAMBL/HNRNPD_protein_hg38.html)

-

-

-

-View all variants in GenomePaint [hg19](https://morinlab.github.io/LLMPP/GAMBL/HNRNPD.html) or [hg38](https://morinlab.github.io/LLMPP/GAMBL/HNRNPD_hg38.html)

-

-

-

-## HNRNPD Expression

-

-

-

-<!-- FLAGGED FOR TIER 2 -->

-<!-- ORIGIN: Unknown -->

-

-## References

-| |2 |relevance in BL not firmly established|

-1. Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, Richards KL, Dunphy CH, Choi WWL, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers CR, Naresh KN, Evens AM, Chadburn A, Gordon LI, Czader MB, Gill JI, Hsi ED, Greenough A, Moffitt AB, McKinney M, Banerjee A, Grubor V, Levy S, Dunson DB, Dave SS. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012 Dec;44(12):1321–1325. PMCID: PMC3674561

-| |2-a | aSHM target; Although recurrent, the relevance of mutations in DLBCL is tenuous |

-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. PMCID: PMC6167379

-| |2 |relevance in FL not firmly established|

-||2|relevance in PMBL/cHL/GZL not firmly established|

-| |2 |relevance in DLBCL not firmly established|

-1. Reddy A, Zhang J, Davis NS, Moffitt AB, Love CL, Waldrop A, Leppa S, Pasanen A, Meriranta L, Karjalainen-Lindsberg ML, Nørgaard P, Pedersen M, Gang AO, Høgdall E, Heavican TB, Lone W, Iqbal J, Qin Q, Li G, Kim SY, Healy J, Richards KL, Fedoriw Y, Bernal-Mizrachi L, Koff JL, Staton AD, Flowers CR, Paltiel O, Goldschmidt N, Calaminici M, Clear A, Gribben J, Nguyen E, Czader MB, Ondrejka SL, Collie A, Hsi ED, Tse E, Au-Yeung RKH, Kwong YL, Srivastava G, Choi WWL, Evens AM, Pilichowska M, Sengar M, Reddy N, Li S, Chadburn A, Gordon LI, Jaffe ES, Levy S, Rempel R, Tzeng T, Happ LE, Dave T, Rajagopalan D, Datta J, Dunson DB, Dave SS. Genetic and Functional Drivers of Diffuse Large B Cell Lymphoma. Cell. 2017 Oct;171(2):481-494.e15.

-2. Tiacci E, Ladewig E, Schiavoni G, Penson A, Fortini E, Pettirossi V, Wang Y, Rosseto A, Venanzi A, Vlasevska S, Pacini R, Piattoni S, Tabarrini A, Pucciarini A, Bigerna B, Santi A, Gianni AM, Viviani S, Cabras A, Ascani S, Crescenzi B, Mecucci C, Pasqualucci L, Rabadan R, Falini B. Pervasive mutations of JAK-STAT pathway genes in classical Hodgkin lymphoma. Blood. 2018 May 31;131(22):2454–2465. PMCID: PMC6634958

-| |2 |relevance in BL not firmly established|

-1. Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, Richards KL, Dunphy CH, Choi WWL, Srivastava G, Lugar PL, Rizzieri DA, Lagoo AS, Bernal-Mizrachi L, Mann KP, Flowers CR, Naresh KN, Evens AM, Chadburn A, Gordon LI, Czader MB, Gill JI, Hsi ED, Greenough A, Moffitt AB, McKinney M, Banerjee A, Grubor V, Levy S, Dunson DB, Dave SS. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012 Dec;44(12):1321–1325. PMCID: PMC3674561