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| Status |
Public on May 31, 2023 |
| Title |
Genome-wide single nucleotide polymorphism analysis identifies DNA variations predictive of R-CHOP efficacy in diffuse large B-cell lymphoma |
| Organism |
Homo sapiens |
| Experiment type |
SNP genotyping by SNP array
Genome variation profiling by SNP array
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| Summary |
R-CHOP standard chemotherapy is successful in about 60% of patients with diffuse large B-cell lymphoma (DLBCL). Patients who do not benefit from it, due to tumor drug resistance, have a poor prognosis. To date, the available predictive biomarkers mainly relate to prognosis. We conducted the first prospective GWAS clinical study appositely designed to identify constitutional biomarkers predictive of R-CHOP efficacy and toxicity. Overall, 217 any stage chemonaive DLBCL patients candidate to R-CHOP were enrolled. ~800000 SNPs were analysed by the UK Biobank Axiom Array. Median age of eligible pts was 59.2 years, women were 49.7%. 45.4% of pts were in stage I-II. According to the revised IPI (R-IPI), 14.1%, 56.8% and 29.2% were in the very good (0), good (1-2) and poor (3-5) prognosis groups, respectively. 85.9% of pts obtained CR to R-CHOP. Based on the results obtained, we were able to build a seven-SNP score by summing the number of deleterious alleles from the SNPs for which highly significant associations with PFS were achieved. Wild-type patients showed a prolonged PFS compared with patients carrying 1 deleterious allele or 2+ deleterious alleles (p<0.001). When the score was applied to patients stratified according to R-IPI, wild-type patients classified as R-IPI 1-2 and R-IPI 3-5 showed a prolonged PFS compared with patients with the same respective R-IPI score carrying 1 deleterious allele or 2+ deleterious alleles (p<0.001). After a proper validation in an independent cohort of patients, the seven-SNP risk score could be proposed to select patients to whom offer a more aggressive treatment as well as an additional factor to those currently included in the R-IPI that could successfully contribute to predict response to R-CHOP.
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| Overall design |
Affymetrix SNP arrays were performed on 187 constitutional DNA samples from adult DLBCL patients (two samples did not pass the quality control of genotypic data). Overall, 185 samples are provided.
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| Contributor(s) |
Perrone G, Rigacci L, Urru S, Kovalchuk S, Brugia M, Fabbri A, Iovino L, Puccini B, Cencini E, Orciuolo E, Birtolo S, Melosi A, Santini S, Landini I, Roviello G, Chiorino G, Bosi A, Bocchia M, Petrini M, Mini E, Nobili S |
| Citation |
https://doi.org/10.3390/cancers15102753
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| Submission date |
Oct 22, 2021 |
| Last update date |
Jun 01, 2023 |
| Contact name |
Stefania Nobili |
| E-mail(s) |
stefania.nobili@unifi.it
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| Organization name |
University of Florence
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| Department |
Health Sciences
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| Street address |
viale Pieraccini 6
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| City |
Firenze |
| ZIP/Postal code |
50139 |
| Country |
Italy |
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| Platforms (1) |
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| Samples (185)
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| Relations |
| BioProject |
PRJNA773793 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE186441_AxiomGT1_genotype_calls3.txt.gz |
34.6 Mb |
(ftp)(http) |
TXT |
| GSE186441_AxiomGT1_intensity.txt.gz |
1.4 Gb |
(ftp)(http) |
TXT |
| GSE186441_RAW.tar |
2.2 Gb |
(http)(custom) |
TAR (of CEL) |
| Processed data are available on Series record |
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