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| Status |
Public on Dec 19, 2023 |
| Title |
Unravelling the heterogeneous molecular landscape of pediatric post-transplant lymphoproliferative disorders |
| Platform organisms |
Homo sapiens; Mus musculus |
| Sample organism |
Homo sapiens |
| Experiment type |
SNP genotyping by SNP array
Genome variation profiling by SNP array
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| Summary |
It is unknown whether pediatric monomorphic post-transplant lymphoproliferative disorders (mPTLD) display similar genetic features than the immunocompetent counterpart and if they resemble adult mPTLD. We have investigated 39 pediatric mPTLD, 33 diffuse large B-cell lymphoma (DLBCL) and six Burkitt lymphoma (BL), by an integrated approach, including fluorescence in situ hybridization, cell of origin determination (COO), targeted gene sequencing and copy-number arrays. According to COO, 24/28 DLBCL (86%) were classified as activated B-cell (ABC) and all six BL were germinal center B cell (GCB)-type. Thirty-three out of 37 investigated mPTLD were positive for EBV infection. Overall, PTLD-BL carried mutations in MYC in addition to ID3 and DDX3X, ARID1A or CCND3 and a higher mutational burden than PTLD-DLBCL (12.3 vs 6.2, P = 0.01). CN profile of PTLD-BL was less complex than in IC-BL (1 vs 6.26; P < 0.005). PTLD-DLBCL showed a very heterogeneous genomic profile characterized by a lower number of mutations (2.4 vs 6.5, P=0.01) and less CNA (2.10 vs 4.36 ; P < 0.05) than in IC patients. Pathway enrichment analysis revealed that epigenetic modifiers and Notch pathway (4 cases each) were the most recurrently affected. In conclusion, these findings further unravel for the first time the molecular heterogeneity of pediatric mPTLD and provide new parameters for the design of more effective therapeutic strategies.
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| Overall design |
Thirty-nine monomorphic PTLD <19 years-old (mean 10y, gender 25 male/14 female) were recruited and analyzed for germinal center markers, IRF4 and EBER expression. Presence of MYC, PAX5, IRF4, BCL2, BCL6 and 11q alterations was investigated by FISH. Additional molecular studies included clonality, copy number (CN) arrays, cell of origin-COO (Nanostring) and mutational analyses (Custom 167 lymphoma related genes panel, SureSelectXT, Agilent).
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| Contributor(s) |
Salmeron Villalobos J, Castrejon de Anta N, Balagué O, Salaverria I |
| Citation(s) |
37053555 |
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| Submission date |
Mar 09, 2022 |
| Last update date |
Dec 20, 2023 |
| Contact name |
Itziar Salaverria |
| E-mail(s) |
isalaver@clinic.cat
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| Organization name |
Hospital Clínic
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| Street address |
Rossello 153
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| City |
Barcelona |
| ZIP/Postal code |
08036 |
| Country |
Spain |
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| Platforms (2) |
| GPL18602 |
[OncoScan] Affymetrix OncoScan FFPE Assay |
| GPL18603 |
Illumina Hiseq 1000 (Mus musculus) |
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| Samples (26)
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| GSM5942277 |
Postransplant lymphoproliferative disorder (PTLD) 2 |
| GSM5942278 |
Postransplant lymphoproliferative disorder (PTLD) 7 |
| GSM5942279 |
Postransplant lymphoproliferative disorder (PTLD) 10 |
| GSM5942280 |
Postransplant lymphoproliferative disorder (PTLD) 11 |
| GSM5942281 |
Postransplant lymphoproliferative disorder (PTLD) 12 |
| GSM5942282 |
Postransplant lymphoproliferative disorder (PTLD) 13 |
| GSM5942283 |
Postransplant lymphoproliferative disorder (PTLD) 14 |
| GSM5942284 |
Postransplant lymphoproliferative disorder (PTLD) 15 |
| GSM5942285 |
Postransplant lymphoproliferative disorder (PTLD) 19 |
| GSM5942286 |
Postransplant lymphoproliferative disorder (PTLD) 20 |
| GSM5942287 |
Postransplant lymphoproliferative disorder (PTLD) 21 |
| GSM5942288 |
Postransplant lymphoproliferative disorder (PTLD) 22 |
| GSM5942289 |
Postransplant lymphoproliferative disorder (PTLD) 25 |
| GSM5942290 |
Postransplant lymphoproliferative disorder (PTLD) 26 |
| GSM5942291 |
Postransplant lymphoproliferative disorder (PTLD) 28 |
| GSM5942292 |
Postransplant lymphoproliferative disorder (PTLD) 29 |
| GSM5942293 |
Postransplant lymphoproliferative disorder (PTLD) 30 |
| GSM5942294 |
Postransplant lymphoproliferative disorder (PTLD) 31 |
| GSM5942295 |
Postransplant lymphoproliferative disorder (PTLD) 32 |
| GSM5942296 |
Postransplant lymphoproliferative disorder (PTLD) 33 |
| GSM5942297 |
Postransplant lymphoproliferative disorder (PTLD) 36 |
| GSM5942298 |
Postransplant lymphoproliferative disorder (PTLD) 37 |
| GSM5942299 |
Postransplant lymphoproliferative disorder (PTLD) 38 |
| GSM5942300 |
Postransplant lymphoproliferative disorder (PTLD) 39 |
| GSM5942301 |
Postransplant lymphoproliferative disorder (PTLD) 42 |
| GSM5942302 |
Postransplant lymphoproliferative disorder (PTLD) 43 |
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| Relations |
| BioProject |
PRJNA814282 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE198253_Processed_Oncoscan_PTLD_DATA.xlsx |
17.5 Kb |
(ftp)(http) |
XLSX |
| GSE198253_RAW.tar |
629.9 Mb |
(http)(custom) |
TAR (of CEL, OSCHP) |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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