GNA13

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bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true

GNA13

Overview

Mutations in GNA13, which encodes a G protein alpha subunit involved in multiple signaling pathways, have been identified as significant contributors to the pathogenesis of germinal centre-derived B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL).¹ This gene has some recurrent sites of mutations (hot spots). Overall, mutations are often loss-of-function in nature, disrupting the normal activity of GNA13. GNA13 regulates B-cell homing and growth suppression within the germinal center niche and its loss of function promotes lymphoma development.²

History

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timeline
    title Publication timing
      2011-07-27 : Morin : FL
      2012-12-01 : Love : BL
      2015-02-12 : Reichel : PMBL

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Relevance tier by entity

Entity	Tier	Description
	1	high-confidence PMBL/cHL/GZL gene[@reichelFlowSortingExome2015a]
	1	high-confidence BL gene [@loveGeneticLandscapeMutations2012]
	1	high-confidence DLBCL gene[@morinFrequentMutationHistonemodifying2011]
	1	high-confidence FL gene [@morinFrequentMutationHistonemodifying2011]

Mutation incidence in large patient cohorts (GAMBL reanalysis)

Entity	source	frequency (%)
BL	GAMBL genomes+capture	21.02
BL	Thomas cohort	21.60
BL	Panea cohort	20.80
DLBCL	GAMBL genomes	11.66
DLBCL	Schmitz cohort	8.51
DLBCL	Reddy cohort	11.91
DLBCL	Chapuy cohort	10.26
FL	GAMBL genomes	10.16

Mutation pattern and selective pressure estimates

Entity	aSHM	Significant selection	dN/dS (missense)	dN/dS (nonsense)
BL	No	Yes	51.517	966.741
DLBCL	No	Yes	38.484	284.077
FL	No	Yes	48.688	215.216

GNA13 Hotspots

Chromosome	Coordinate (hg19)	ref>alt	HGVSp
chr17	63052633	G>A	Q27*
chr17	63052631	C>G	Q27H
chr17	63052630	G>A	Q28*
chr17	63052613	C>G	E33D
chr17	63052609	C>G	D35H

View coding variants in ProteinPaint hg19 or hg38

View all variants in GenomePaint hg19 or hg38

GNA13 Expression

References

1. Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, Johnson NA, Severson TM, Chiu R, Field M, Jackman S, Krzywinski M, Scott DW, Trinh DL, Tamura-Wells J, Li S, Firme MR, Rogic S, Griffith M, Chan S, Yakovenko O, Meyer IM, Zhao EY, Smailus D, Moksa M, Chittaranjan S, Rimsza L, Brooks-Wilson A, Spinelli JJ, Ben-Neriah S, Meissner B, Woolcock B, Boyle M, McDonald H, Tam A, Zhao Y, Delaney A, Zeng T, Tse K, Butterfield Y, Birol I, Holt R, Schein J, Horsman DE, Moore R, Jones SJM, Connors JM, Hirst M, Gascoyne RD, Marra MA. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011 Jul 27;476(7360):298–303. PMCID: PMC3210554
2. Muppidi JR, Schmitz R, Green JA, Xiao W, Larsen AB, Braun SE, An J, Xu Y, Rosenwald A, Ott G, Gascoyne RD, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Vaidehi N, Staudt LM, Cyster JG. Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma. Nature. 2014 Dec 11;516(7530):254-8. doi: 10.1038/nature13765. Epub 2014 Sep 28. PMID: 25274307; PMCID: PMC4267955.
3. 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
4. Reichel J, Chadburn A, Rubinstein PG, Giulino-Roth L, Tam W, Liu Y, Gaiolla R, Eng K, Brody J, Inghirami G, Carlo-Stella C, Santoro A, Rahal D, Totonchy J, Elemento O, Cesarman E, Roshal M. Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood. 2015 Feb 12;125(7):1061–1072. PMID: 25488972