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Clinical implications of cytogenetic heterogeneity in multiple myeloma patients with TP53 deletion.

ABSTRACT: TP53 deletion (?TP53) in myeloma is known to be a high-risk finding associated with poorer prognosis. The prognostic impact of underlying cytogenetic heterogeneity in patients with myeloma associated with ?TP53 is unknown. We studied 90 patients with myeloma associated with ?TP53 identified by interphase fluorescence in situ hybridization and assessed the impact of karyotype and coexisting alterations of IGH, RB1, and CKS1B. There were 54 men and 36 women with a median age of 59 years (range 38-84); 14 patients had a normal karyotype (NK/?TP53), 73 had a complex karyotype (CK/?TP53), and 3 had a non-complex abnormal karyotype. Patients with CK/?TP53 showed a significantly poorer overall survival compared with patients with NK/?TP53 (P=0.0243). Furthermore, in the CK/?TP53 group, patients with IGH rearrangement other than t(11;14)(q13;q32)/CCND1-IGH, designated as adverse-IGH, had an even worse outcome (P=0.0045). In contrast, RB1 deletion, CKS1B gain, ploidy, additional chromosome 17 abnormalities, or ?TP53 clone size did not impact prognosis. Stem cell transplant did not improve overall survival in either the NK/?TP53 or CK/?TP53 (P=0.8810 and P=0.1006) groups, but tandem stem cell transplant did improve the overall survival of patients with CK/?TP53 (P=0.0067). Multivariate analysis confirmed in this cohort that complex karyotype (hazard ratio 1.976, 95% CI 1.022-3.821, P=0.043), adverse-IGH (hazard ratio 3.126, 95% CI 1.192-8.196, P=0.020), and tandem stem cell transplant independently correlate with overall survival (hazard ratio 0.281, 95% CI 0.091-0.866, P=0.027). We conclude that comprehensive genetic assessment adds to TP53 status in the risk stratification of myeloma patients.

SUBMITTER: Hao S

PROVIDER: S-EPMC5628266 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Clinical implications of cytogenetic heterogeneity in multiple myeloma patients with TP53 deletion.

Hao Suyang S Lin Pei P Medeiros L Jeffrey LJ Fang Lianghua L Carballo-Zarate Adrian A AA Konoplev Sergej N SN Sargent Rachel L RL Weber Donna M DM Thomas Sheeba K SK Manasanch Elisabet E EE Orlowski Robert Z RZ Lu Xinyan X

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20170630 10

TP53 deletion (ΔTP53) in myeloma is known to be a high-risk finding associated with poorer prognosis. The prognostic impact of underlying cytogenetic heterogeneity in patients with myeloma associated with ΔTP53 is unknown. We studied 90 patients with myeloma associated with ΔTP53 identified by interphase fluorescence in situ hybridization and assessed the impact of karyotype and coexisting alterations of IGH, RB1, and CKS1B. There were 54 men and 36 women with a median age of 59 years (range 38- ...[more]

PMID: 28664940

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Project description:BackgroundMultiple myeloma (MM) is a disease characterized by heterogeneous clinical presentations as well as complex genetic and molecular abnormalities. In MM, cytogenetic analysis is a challenge because of the low proliferation of malignant plasma cells. Thus, interphase fluorescence in situ hybridization (FISH), performed on sorted plasma cells detected abnormalities independently of a proliferative and infiltrative index. The purpose of this study was to explore, for the first time, the cytogenetic and molecular genetics features in Moroccan patients with multiple myeloma referred exclusively to National Reference Laboratory and to determine their risk stratification based on these features.MethodsWe performed cytogenetic analysis on 93 MM cases, all patients were subjected to FISH analysis, among which 45 patients have benefited from both FISH analysis and standard karyotype.ResultsKaryotype was normal in 78% (35/45) while, it was complex with varied structural and numerical abnormalities in 22% (10/45) of all patients, among which Hyperdiploid karyotype was found in 9% (n = 4 cases) and nonhyperdiploid in 13% (n = 6 cases). The most common numerical abnormalities were gains of chromosomes 3, 5, 9, 15, and 19. Whole chromosome losses were also frequent, affecting chromosomes X, 3, 14, 16 and 22. FISH analysis detected abnormalities in 50% of cases. The translocation t(4;14) and dup (1q) were the most frequent types of anomalies (14% and 13% respectively), followed by (17p) deletion and 14q32/IGH translocations with an undetermined origin (12% each) then the (1p) deletion (4%). For the normal karyotypes, FISH revealed chromosome abnormalities in 46%.ConclusionThis study compares the results of cytogenetic analysis of chromosomal abnormalities in the Moroccan population with other countries. ½ patient showed at least one type of molecular genetic abnormalities. Therefore, the introducing of the cytogenetic analysis is obligatory in the diagnosis of multiple myeloma.

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Clinical implications of cytogenetic heterogeneity in multiple myeloma patients with TP53 deletion.

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Clinical implications of cytogenetic heterogeneity in multiple myeloma patients with TP53 deletion.

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