Primary vitreoretinal lymphomas display a remarkably restricted immunoglobulin gene repertoire.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
14 04 2020
14 04 2020
Historique:
received:
16
09
2019
accepted:
17
01
2020
entrez:
9
4
2020
pubmed:
9
4
2020
medline:
15
5
2021
Statut:
ppublish
Résumé
Primary vitreoretinal lymphoma (PVRL) is a high-grade lymphoma affecting the vitreous and/or the retina. The vast majority of cases are histopathologically classified as diffuse large B-cell lymphoma (DLBCL) and considered a subtype of primary central nervous system lymphoma (PCNSL). To obtain more insight into the ontogenetic relationship between PVRL and PCNSL, we adopted an immunogenetic perspective and explored the respective immunoglobulin gene repertoire profiles from 55 PVRL cases and 48 PCNSL cases. In addition, considering that both entities are predominantly related to activated B-cell (ABC) DLBCL, we compared their repertoire with that of publicly available 262 immunoglobulin heavy variable domain gene rearrangement sequences from systemic ABC-type DLBCLs. PVRL displayed a strikingly biased repertoire, with the IGHV4-34 gene being used in 63.6% of cases, which was significantly higher than in PCNSL (34.7%) or in DLBCL (30.2%). Further repertoire bias was evident by (1) restricted associations of IGHV4-34 expressing heavy chains, with κ light chains utilizing the IGKV3-20/IGKJ1 gene pair, including 5 cases with quasi-identical sequences, and (2) the presence of a subset of stereotyped IGHV3-7 rearrangements. All PVRL IGHV sequences were highly mutated, with evidence of antigen selection and ongoing mutations. Finally, half of PVRL and PCNSL cases carried the MYD88 L265P mutation, which was present in all 4 PVRL cases with stereotyped IGHV3-7 rearrangements. In conclusion, the massive bias in the immunoglobulin gene repertoire of PVRL delineates it from PCNSL and points to antigen selection as a major driving force in their development.
Identifiants
pubmed: 32267931
pii: S2473-9529(20)31397-5
doi: 10.1182/bloodadvances.2019000980
pmc: PMC7160258
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1357-1366Informations de copyright
© 2020 by The American Society of Hematology.
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