Combining MYD88 L265P mutation detection and clonality determination on CSF cellular and cell‐free DNA improves diagnosis of primary CNS lymphoma
Abstract
Diagnosis of primary central nervous system lymphoma (PCNSL) is challenging, and although brain biopsy remains the gold standard, cerebrospinal f luid (CSF) con-stitutes a less invasive source of lymphomatous biomarkers. In a retrospective co-hort of 54 PCNSL cases tested at diagnosis or relapse, we evaluated the contribution of immunoglobulin heavy chain (IGH) gene clonality and MYD88 L265P detection on both CSF cell pellets and supernatants, in comparison with cytology, f low cy-tometry, interleukin (IL)-10 and IL-6 quantification. Clonality assessment included a new assay to detect partial IGH-DJ rearrangements. Clonal IGH rearrangements a nd/or MYD88 L265P mutation were detected in 27 (50%) cell pellets and 24 (44%) supernatant cell-free (cf) DNA. Combining analyses on both compartments, 36 (66%) cases had at least one detectable molecular marker, present only in cf DNA for 9 (16%) of them. While cytology and f low cytometry were positive in only 7 (13.0%) and 9 (17.3%) cases respectively, high IL-10 levels were observed in 36 (66.7%) cases. Overall, taking into account molecular and cytokine results, 46/54 (85%) cases had at least one lymphomatous biomarker detectable in the CSF. These results show that this combination of biomarkers evaluated on both cell pellet and supernatant CSF fractions improves significantly the biological diagnosis of PCNSL.
Keywords
primary central nervous system lymphoma
PCR
polymerase chain reaction
RFLP
restriction fragment length polymorphism
SHM
CBA
cytometric bead array cfDNA
cell-free DNA CSF
cerebrospinal fluid ctDNA
circulating tumor DNA ddPCR
digital droplet polymerase chain reaction DLBCL
diffuse large B-cell lymphoma FCM
flow cytometry FR
framework regions IG
immunoglobulin IGH
immunoglobulin heavy chain IL
interleukins LOC
lymphomes oculo-cerebraux NGS
next-generation sequencing PCNSL
primary central nervous system lymphoma PCR
polymerase chain reaction RFLP
restriction fragment length polymorphism SHM
somatic hypermutation clonality
CNS lymphoma
CSF
MYD88
cytometric bead array
cfDNA
cell-free DNA
cerebrospinal fluid
ctDNA
circulating tumor DNA
ddPCR
digital droplet polymerase chain reaction
DLBCL
diffuse large B-cell lymphoma
FCM
flow cytometry
FR
framework regions
IG
immunoglobulin
IGH
immunoglobulin heavy chain
IL
interleukins
LOC
lymphomes oculo-cerebraux
NGS
next-generation sequencing
PCNSL
Domains
Human genetics
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