Techniques for detecting chromosomal aberrations in myelodysplastic syndromes

Song, Qibin; Peng, Min; Chu, Yuxin; Huang, Shiang

doi:10.18632/oncotarget.17698

Cited by 7 publications

(8 citation statements)

References 116 publications

(123 reference statements)

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“…Nevertheless, the wide CI in this study highlights the need for validation with a larger sample. Although genome sequencing is an expensive and highly specialized assay technique, chromosomal deletion can be assessed with Fluorescence in situ hybridization (FISH) or spectral karyotyping (SKY) (102). In this regard, it is worth mentioning that Zenonos et al present one of the few prospective studies with a strong statistical design (36).…”

Section: Discussionmentioning

confidence: 99%

Prognostic molecular biomarkers in chordomas: A systematic review and identification of clinically usable biomarker panels

Rubino

Alvarez‐Breckenridge²,

Akdemir³

et al. 2022

Front. Oncol.

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Introduction and objectiveDespite the improvements in management and treatment of chordomas over time, the risk of disease recurrence remains high. Consequently, there is a push to develop effective systemic therapeutics for newly diagnosed and recurrent disease. In order to tailor treatment for individual chordoma patients and develop effective surveillance strategies, suitable clinical biomarkers need to be identified. The objective of this study was to systematically review all prognostic biomarkers for chordomas reported to date in order to classify them according to localization, study design and statistical analysis.MethodsUsing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed published studies reporting biomarkers that correlated with clinical outcomes. We included time-to-event studies that evaluated biomarkers in skull base or spine chordomas. To be included in our review, the study must have analyzed the outcomes with univariate and/or multivariate methods (log-rank test or a Cox-regression model).ResultsWe included 68 studies, of which only 5 were prospective studies. Overall, 103 biomarkers were analyzed in 3183 patients. According to FDA classification, 85 were molecular biomarkers (82.5%) mainly located in nucleus and cytoplasm (48% and 27%, respectively). Thirty-four studies analyzed biomarkers with Cox-regression model. Within these studies, 32 biomarkers (31%) and 22 biomarkers (21%) were independent prognostic factors for PFS and OS, respectively.ConclusionOur analysis identified a list of 13 biomarkers correlating with tumor control rates and survival. The future point will be gathering all these results to guide the clinical validation for a chordoma biomarker panel. Our identified biomarkers have strengths and weaknesses according to FDA’s guidelines, some are affordable, have a low-invasive collection method and can be easily measured in any health care setting (RDW and D-dimer), but others molecular biomarkers need specialized assay techniques (microRNAs, PD-1 pathway markers, CDKs and somatic chromosome deletions were more chordoma-specific). A focused list of biomarkers that correlate with local recurrence, metastatic spread and survival might be a cornerstone to determine the need of adjuvant therapies.

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Section: Discussionmentioning

confidence: 99%

Prognostic molecular biomarkers in chordomas: A systematic review and identification of clinically usable biomarker panels

Rubino

Alvarez‐Breckenridge²,

Akdemir³

et al. 2022

Front. Oncol.

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“…With the FISH results it was possible to note that this chromosomal abnormality was not a simple reciprocal translocation involving the regions of chromosomes 9p24 and 11q22, but an unbalanced chromosomal alteration due to the monoallelic loss of ATM and KMT2A genes. FISH continues to be considered an important technique for molecular investigation of small or hidden chromosomal abnormalities [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

An uncommon t(9;11)(p24;q22) with monoallelic loss of ATM and KMT2A genes in a child with myelodysplastic syndrome/acute myeloid leukemia who evolved from Fanconi anemia

et al. 2018

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BackgroundMyelodysplastic syndrome (MDS) is rare in the pediatric age group and it may be associated with inheritable bone marrow failure (BMF) such as Fanconi anemia (FA). FA is a rare multi-system genetic disorder, characterized by congenital malformations and progressive BMF. Patients with FA usually present chromosomal aberrations when evolving to MDS or acute myeloid leukemia (AML). Thus, the cytogenetic studies in the bone marrow (BM) of these patients have an important role in the therapeutic decision, mainly in the indication for hematopoietic stem cell transplantation (HSCT). The most frequent chromosomal alterations in the BM of FA patients are gains of the chromosomal regions 1q and 3q, and partial or complete loss of chromosome 7. However, the significance and the predictive value of such clonal alterations, with respect to malignant progress, are not fully understood and data from molecular cytogenetic studies are very limited.Case presentationA five-year-old boy presented recurrent infections and persistent anemia. The BM biopsy revealed hypocellularity. G-banding was performed on BM cells and showed a normal karyotype. The physical examination showed to be characteristic of FA, being the diagnosis confirmed by DEB test. Five years later, even with supportive treatment, the patient presented severe hypocellularity and BM evolution revealing megakaryocyte dysplasia, intense dyserythropoiesis, and 11% myeloblasts. G-banded analysis showed an abnormal karyotype involving a der(9)t(9;11)(p24;q?22). The FISH analysis showed the monoallelic loss of ATM and KMT2A genes. At this moment the diagnosis was MDS, refractory anemia with excess of blasts (RAEB). Allogeneic HSCT was indicated early in the diagnosis, but no donor was found. Decitabine treatment was initiated and well tolerated, although progression to AML occurred 3 months later. Chemotherapy induction was initiated, but there was no response. The patient died due to disease progression and infection complications.ConclusionsMolecular cytogenetic analysis showed a yet unreported der(9)t(9;11)(p24;q?22),der(11)t(9;11)(p24;q?22) during the evolution from FA to MDS/AML. The FISH technique was important allowing the identification at the molecular level of the monoallelic deletion involving the KMT2A and ATM genes. Our results suggest that this chromosomal alteration conferred a poor prognosis, being associated with a rapid leukemic transformation and a poor treatment response.

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“…[ 13 ] The iFISH results were interpreted by 2 or more experts in molecular pathology, independently of parallel metaphase karyotype analysis. [ 5 , 8 , 10 , 11 ]…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, the broad genomic features of MDS have been assessed in large trials by fluorescence in situ hybridization (iFISH), single nucleotide polymorphism array, and next-generation sequencing. [ 5 ] For example, iFISH rapidly and reliably detects specific anomalies with direct prognostic implication such as del(5q) and an isolated del(7q), both of which, according to IPSS-R, confer a poor prognosis in MDS. [ 6 , 7 ] However, iFISH probes only detect predefined aberrations, and genetic anomalies beyond their coverage would be completely missed.…”

Section: Introductionmentioning

confidence: 99%

Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization for detecting chromosome abnormalities in myelodysplastic syndromes

Ai¹,

et al. 2021

Medicine

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This study aimed to compare interphase fluorescence in situ hybridization (iFISH) and multiplex ligation dependent probe amplification (MLPA) for identifying genetic changes in myelodysplastic syndromes (MDS). The frequencies of cytogenetic changes in MDS patients treated at the Institute of Hematology and Blood Disease Hospital (China) in 2009 to 2018 were assessed by iFISH based on bone marrow samples. Then, the effectiveness of MLPA in detecting these anomalies was evaluated. Specimens from 287 MDS patients were assessed. A total of 36.9% (103/279) of MDS cases had chromosomal abnormalities detected by iFISH; meanwhile, 44.1% (123/279) harbored ≥1 copy-number variation (CNV) based on MLPA: +8 (n=46), −5 (n = 39), −7 (n = 27), del 20 (n = 32) and del 17 (n = 17). Overall, 0 to 4 aberrations/case were detected by MLPA, suggesting the heterogeneous and complex nature of MDS cytogenetics. There were 29 cases detected by MLPA, which were undetected by FISH or showed low signals. Sixteen of these cases had their risk classification changed due to MLPA detection, including 9 reassigned to the high-risk IPSS-R group. These findings demonstrated that MLPA is highly efficient in assessing cytogenetic anomalies, with data remarkably corroborating FISH findings (overall consistency of 97.1%). The sensitivities of MLPA in detecting +8, −5, −7, del 20 and del 17 were 92.3%, 97.1%, 100%, 100%, and 90%, respectively, with specificities of 95.8%, 97.6%, 97.7%, 97.6%, and 97%, respectively. MLPA represents a reliable approach, with greater efficiency, accuracy, and speed than iFISH in identifying cytogenetic aberrations in MDS.

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Techniques for detecting chromosomal aberrations in myelodysplastic syndromes

Cited by 7 publications

References 116 publications

Prognostic molecular biomarkers in chordomas: A systematic review and identification of clinically usable biomarker panels

Prognostic molecular biomarkers in chordomas: A systematic review and identification of clinically usable biomarker panels

An uncommon t(9;11)(p24;q22) with monoallelic loss of ATM and KMT2A genes in a child with myelodysplastic syndrome/acute myeloid leukemia who evolved from Fanconi anemia

Multiplex ligation-dependent probe amplification and fluorescence in situ hybridization for detecting chromosome abnormalities in myelodysplastic syndromes

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