The molecular hallmarks of primary and secondary vitreoretinal lymphoma
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The molecular hallmarks of primary and secondary vitreoretinal lymphoma. / Bonzheim, Irina; Sander, Philip; Salmeron-Villalobos, Julia; Süsskind, Daniela; Szurman, Peter; Gekeler, Florian; Spitzer, Martin S; Steinhilber, Julia; Kohler, Esther; Büssgen, Melanie; Schittenhelm, Jens; Salaverria, Itziar; Campo, Elias; Coupland, Sarah E; Quintanilla-Martinez, Leticia; Fend, Falko.
in: BLOOD ADV, Jahrgang 6, Nr. 5, 08.03.2022, S. 1598-1607.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The molecular hallmarks of primary and secondary vitreoretinal lymphoma
AU - Bonzheim, Irina
AU - Sander, Philip
AU - Salmeron-Villalobos, Julia
AU - Süsskind, Daniela
AU - Szurman, Peter
AU - Gekeler, Florian
AU - Spitzer, Martin S
AU - Steinhilber, Julia
AU - Kohler, Esther
AU - Büssgen, Melanie
AU - Schittenhelm, Jens
AU - Salaverria, Itziar
AU - Campo, Elias
AU - Coupland, Sarah E
AU - Quintanilla-Martinez, Leticia
AU - Fend, Falko
N1 - Copyright © 2021 American Society of Hematology.
PY - 2022/3/8
Y1 - 2022/3/8
N2 - Vitreoretinal lymphoma (VRL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) considered a variant of primary central nervous system lymphoma (PCNSL). The diagnosis of VRL requires examination of vitreous fluid, but cytologic differentiation from uveitis remains difficult. Because of its rarity and the difficulty in obtaining diagnostic material, little is known about the genetic profile of VRL. The purpose of our study was to investigate the mutational profile of a large series of primary and secondary VRL. Targeted next-generation sequencing using a custom panel containing the most frequent mutations in PCNSL was performed on 34 vitrectomy samples from 31 patients with VRL and negative controls with uveitis. In a subset of cases, genome-wide copy number alterations (CNAs) were assessed using the OncoScan platform. Mutations in MYD88 (74%), PIM1 (71%), CD79B (55%), IGLL5 (52%), TBL1XR1 (48%), ETV6 (45%), and 9p21/CDKN2A deletions (75%) were the most common alterations, with similar frequencies in primary (n = 16), synchronous (n = 3), or secondary (n = 12) VRL. This mutational spectrum is similar to MYD88mut/CD79Bmut (MCD or cluster 5) DLBCL with activation of Toll-like and B-cell receptor pathways and CDKN2A loss, confirming their close relationship. OncoScan analysis demonstrated a high number of CNAs (mean 18.6 per case). Negative controls lacked mutations or CNAs. Using cell-free DNA of vitreous fluid supernatant, mutations present in cellular DNA were reliably detected in all cases examined. Mutational analysis is a highly sensitive and specific tool for the diagnosis of VRL and can also be applied successfully to cell-free DNA derived from the vitreous.
AB - Vitreoretinal lymphoma (VRL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) considered a variant of primary central nervous system lymphoma (PCNSL). The diagnosis of VRL requires examination of vitreous fluid, but cytologic differentiation from uveitis remains difficult. Because of its rarity and the difficulty in obtaining diagnostic material, little is known about the genetic profile of VRL. The purpose of our study was to investigate the mutational profile of a large series of primary and secondary VRL. Targeted next-generation sequencing using a custom panel containing the most frequent mutations in PCNSL was performed on 34 vitrectomy samples from 31 patients with VRL and negative controls with uveitis. In a subset of cases, genome-wide copy number alterations (CNAs) were assessed using the OncoScan platform. Mutations in MYD88 (74%), PIM1 (71%), CD79B (55%), IGLL5 (52%), TBL1XR1 (48%), ETV6 (45%), and 9p21/CDKN2A deletions (75%) were the most common alterations, with similar frequencies in primary (n = 16), synchronous (n = 3), or secondary (n = 12) VRL. This mutational spectrum is similar to MYD88mut/CD79Bmut (MCD or cluster 5) DLBCL with activation of Toll-like and B-cell receptor pathways and CDKN2A loss, confirming their close relationship. OncoScan analysis demonstrated a high number of CNAs (mean 18.6 per case). Negative controls lacked mutations or CNAs. Using cell-free DNA of vitreous fluid supernatant, mutations present in cellular DNA were reliably detected in all cases examined. Mutational analysis is a highly sensitive and specific tool for the diagnosis of VRL and can also be applied successfully to cell-free DNA derived from the vitreous.
U2 - 10.1182/bloodadvances.2021004212
DO - 10.1182/bloodadvances.2021004212
M3 - SCORING: Journal article
C2 - 34448823
VL - 6
SP - 1598
EP - 1607
JO - BLOOD ADV
JF - BLOOD ADV
SN - 2473-9529
IS - 5
ER -
