Concurrent TP53 and CDKN2A Gene Aberrations in Newly Diagnosed Mantle Cell Lymphoma Correlate with Chemoresistance and Call for Innovative Upfront Therapy
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients’ Characteristics
2.2. Fluorescence in Situ Hybridization (FISH)
2.3. TP53 and CDKN2A Mutation Assessment by Next-Generation Sequencing (NGS)
2.4. Statistical Analysis
3. Results
3.1. Baseline Characteristics of the Analyzed Patients
3.2. Correlation of Baseline Clinical and Histopathological Parameters on Survival in the Cohort of 126 Patients with ≥5% BM Involvement
4. Discussion
4.1. TP53 Deletions and Mutations
4.2. Survival Analysis
4.3. Concurrent Aberration of TP53 and Deletion of CDKN2A Is Associated with Chemoresistance
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Cohort | 126 Patients with Bone Marrow Involvement ≥5% | 97 Patients with No Available Diagnostic Samples | ||
---|---|---|---|---|
Numbers (N) or percentages (%) | N | % | N | % |
All patients | 126 | 57 | 97 | 43 |
M | 88 | 70 | 73 | 75 |
F | 38 | 30 | 24 | 25 |
Age (median; years) | 68 | 66 | ||
Age (range; years) | 29–82 | 40–87 | ||
<65 years | 47 | 37 | 44 | 45 |
≥65 years | 79 | 63 | 53 | 55 |
Stage I–II | 0 | 0 | 7 | 7 |
Stage III | 0 | 0 | 13 | 13 |
Stage IV | 126 | 100 | 77 | 79 |
Ki-67 ≥ 30% * | 36 | 47 | 38 | 48 |
MIPI 1 | 19 | 15 | 25 | 26 |
MIPI 2 | 29 | 23 | 34 | 35 |
MIPI 3 | 78 | 62 | 38 | 39 |
B-symptoms | 52 | 41 | 32 | 33 |
BM infiltration | 126 | 100 | 73 | 75 |
BM infiltration ≥5% | 126 | 100 | 25 | 26 |
Nodal involvement | 108 | 86 | 88 | 91 |
Splenomegaly | 89 | 71 | 46 | 47 |
Extra-hematological involvement | 50 | 40 | 47 | 48 |
Bulky disease (≥5 cm) | 45 | 36 | 27 | 28 |
CNS involvement ** | 17 | 13 | 7 | 7 |
Intensified therapy | 37 | 29 | 50 | 52 |
R-CHOP-like therapy | 71 | 56 | 38 | 39 |
Palliative therapy | 8 | 6 | 7 | 7 |
Watch and wait | 7 | 6 | 1 | 1 |
Died before initiation of therapy | 3 | 2 | 0 | 0 |
Died during induction | 9 | 7 | 0 | 0 |
ORR (CR/PR) | 90 | 71 | 92 | 95 |
CR | 61 | 48 | 73 | 75 |
PR | 29 | 23 | 19 | 20 |
SD | 4 | 3 | 3 | 3 |
PD | 15 | 12 | 0 | 0 |
Event | 78 | 62 | 32 | 33 |
Relapse | 48 | 38 | 18 | 19 |
Death ** | 55 | 44 | 21 | 22 |
CDK4 | RB1 | BCL2 | ATM | TP53 | CDKN2A | MYC | |
---|---|---|---|---|---|---|---|
CDK4 | 1 | 0.138 | <0.001 | 0.260 | 0.651 | 0.016 | 0.055 |
RB1 | 1 | 0.384 | 0.847 | 0.191 | <0.001 | 0.074 | |
BCL2 | 1 | 0.091 | 0.965 | 0.012 | 0.055 | ||
ATM | 1 | 0.164 | 0.05 | 0.706 | |||
TP53 | 1 | 0.006 | 0.071 | ||||
CDKN2A | 1 | 0.065 | |||||
MYC | 1 |
A. Event-Free Survival | B. Overall Survival | ||||||
---|---|---|---|---|---|---|---|
Gene | HR | 95% CI | p | Gene | HR | 95% CI | p |
CDK4 | 1.6 | 0.8–3.1 | 0.218 | CDK4 | 1.7 | 0.8–3.7 | 0.205 |
RB1 | 0.9 | 0.5–1.6 | 0.803 | RB1 | 1.2 | 0.6–2.2 | 0.645 |
BCL2 | 1.5 | 0.8–2.5 | 0.287 | BCL2 | 2.6 | 1.4–4.8 | 0.004 |
ATM | 1.1 | 0.7–1.9 | 0.667 | ATM | 1.0 | 0.6–2.0 | 0.921 |
TP53 | 2.3 | 1.4–3.6 | 0.001 | TP53 | 2.2 | 1.2–3.8 | 0.008 |
CDKN2A | 2.6 | 1.5–4.7 | 0.001 | CDKN2A | 2.5 | 1.2–4.9 | 0.011 |
MYC | 1.6 | 1.0–2.6 | 0.06 | MYC | 1.2 | 0.7–2.2 | 0.507 |
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Malarikova, D.; Berkova, A.; Obr, A.; Blahovcova, P.; Svaton, M.; Forsterova, K.; Kriegova, E.; Prihodova, E.; Pavlistova, L.; Petrackova, A.; et al. Concurrent TP53 and CDKN2A Gene Aberrations in Newly Diagnosed Mantle Cell Lymphoma Correlate with Chemoresistance and Call for Innovative Upfront Therapy. Cancers 2020, 12, 2120. https://doi.org/10.3390/cancers12082120
Malarikova D, Berkova A, Obr A, Blahovcova P, Svaton M, Forsterova K, Kriegova E, Prihodova E, Pavlistova L, Petrackova A, et al. Concurrent TP53 and CDKN2A Gene Aberrations in Newly Diagnosed Mantle Cell Lymphoma Correlate with Chemoresistance and Call for Innovative Upfront Therapy. Cancers. 2020; 12(8):2120. https://doi.org/10.3390/cancers12082120
Chicago/Turabian StyleMalarikova, Diana, Adela Berkova, Ales Obr, Petra Blahovcova, Michael Svaton, Kristina Forsterova, Eva Kriegova, Eva Prihodova, Lenka Pavlistova, Anna Petrackova, and et al. 2020. "Concurrent TP53 and CDKN2A Gene Aberrations in Newly Diagnosed Mantle Cell Lymphoma Correlate with Chemoresistance and Call for Innovative Upfront Therapy" Cancers 12, no. 8: 2120. https://doi.org/10.3390/cancers12082120