Publications by authors named "Aiko Sato-Otsubo"
Novel therapeutic strategies are urgently required for osteosarcoma, given the early age at onset and persistently high mortality rate. Modern transcriptomics techniques can identify differentially expressed genes (DEGs) that may serve as biomarkers and therapeutic targets, so we screened for DEGs in osteosarcoma. We found that osteosarcoma cases could be divided into fair and poor survival groups based on gene expression profiles.
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- * Multiomics analysis showed MNKPL is distinct from other leukemia types and suggested that both NK and myeloid cells may originate from shared progenitor cells.
- * Current treatments for MNKPL are not very effective, but the study found that MNKPL is especially sensitive to the drug l-asparaginase, which aligns with clinical observations of its effectiveness in patients.
Stem cell gene therapy using the MFGS-gp91 retroviral vector was performed on a 27-year-old patient with X-linked chronic granulomatous disease (X-CGD) in 2014. The patient's refractory infections were resolved, whereas the oxidase-positive neutrophils disappeared within 6 months. Thirty-two months after gene therapy, the patient developed myelodysplastic syndrome (MDS), and vector integration into the MECOM locus was identified in blast cells.
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- Second malignant neoplasms (SMNs) are serious complications that can develop after pediatric cancer treatment, and this study investigates the genetic factors that may influence their occurrence.
- The researchers conducted whole-exome sequencing on 14 pediatric patients with SMNs and found that 35.7% had harmful genetic mutations in cancer-predisposing genes, particularly in TP53 and DICER1, which is significantly higher than in a control group.
- The findings suggest that genetic variations, along with treatments like platinum drugs, contribute to the risk of developing secondary cancers, indicating the need for thorough genetic analysis to better predict and manage these risks in pediatric cancer survivors.
Article Synopsis
- Mixed lineage leukemia 1-rearranged (MLL1-r) acute leukemia patients have poor treatment responses, necessitating the development of therapies that disrupt the Menin-MLL1 complex, such as the compound DS-1594a.
- Preclinical evaluations showed that DS-1594a and its salts effectively inhibited the growth of MLL1-r or NPM1c leukemic cells, outperforming traditional chemotherapy like cytrabine in in vitro and in vivo models.
- DS-1594a, with its potent antitumor effects, suggests potential as a new oral anticancer therapy, distinct from existing treatments, offering hope for improved outcomes in acute leukemia patients.
Article Synopsis
- * Researchers identified the PHGDH gene as a key player in aggressive neuroblastomas, particularly in cases with poor prognosis and certain genetic features.
- * Inhibiting serine metabolism via PHGDH and combining it with arginine metabolism inhibitors showed promise in reducing neuroblastoma cell growth, suggesting a new treatment strategy focused on these metabolic pathways.
Article Synopsis
- - KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) is a challenging type of childhood leukemia, and researchers conducted extensive genetic studies on 84 infants with this condition to understand its complexity.
- - The analysis revealed five distinct clusters of the disease, each characterized by different genetic factors and stages of blood cell development, which include various types of IRX and HOXA gene involvement.
- - A key finding is that specific mutations in the RAS pathway can predict patient outcomes, with one subgroup showing a high mutation rate and severe prognosis, emphasizing the need for personalized treatment strategies based on genetic insights.
Quantitative assessment of copy number alterations by liquid biopsy for neuroblastoma.
Genes Chromosomes Cancer
November 2022
Article Synopsis
- Liquid biopsy is a noninvasive method using blood samples to detect genomic changes, offering an alternative to traditional tissue biopsies for patients with neuroblastoma (NB).
- In this study, researchers analyzed cell-free DNA (cfDNA) from 24 NB patients at diagnosis, focusing on MYCN amplification and 11q loss of heterozygosity (11qLOH) using droplet digital PCR (ddPCR).
- The analysis showed a strong correlation (0.88) between MYCN copy numbers in cfDNA and tumor DNA, indicating that cfDNA is a reliable source for assessing these genomic factors in NB patients.
Article Synopsis
- * The fusion protein created from this genetic change shows abnormal activity, promoting cancer cell growth and survival through pathways like ERK, AKT, and STAT3, and is also responsive to ALK inhibitors.
- * This discovery suggests that the TENM3-ALK fusion protein could serve as a new target for therapy and a potential diagnostic marker for neuroblastoma, offering insights into the disease's underlying mechanisms.
Article Synopsis
- The study investigates genetic variation's impact on second malignant neoplasms (SMNs) in children previously treated for leukemia or lymphoma, focusing on NUDT15 gene variants.
- A higher prevalence of NUDT15 hypomorphic variants was found in children with SMNs compared to the general population, suggesting a potential link.
- Treatment with the chemotherapy drug 6-mercaptopurine (6-MP) resulted in increased DNA damage in cells lacking functional NUDT15, indicating these variants may heighten SMN risk in affected patients.
Genetic features of B-cell lymphoblastic lymphoma with TCF3-PBX1.
Cancer Rep (Hoboken)
September 2022
Article Synopsis
- Lymphoblastic lymphoma (LBL) and acute lymphoblastic leukemia (ALL) are related but differ in their molecular genetics, particularly in B-cell cases, which are less understood due to their rarity.
- Researchers conducted whole exome sequencing (WES) on seven patients with TCF3-PBX1-positive B-cell LBL to identify genetic alterations.
- Findings revealed recurrent mutations in the KMT2D gene and 6q loss of heterozygosity, indicating potential relationships with the disease's severity and outcomes, highlighting the need for further comparative studies with B-ALL.
Article Synopsis
- Atypical Burkitt leukemia/lymphoma (preBLL) has distinct molecular features that set it apart from classical Burkitt lymphoma (BL), particularly in their genetic mutations and translocation patterns.
- A case study of an infant with preBLL revealed a mix of characteristics from both preBLL and classical BL, differing in immunophenotyping and genetic mutations.
- The findings suggest that not all preBLL cases are easily distinguishable, highlighting the need for more research to better understand the variations within preBLL.
Article Synopsis
- - Neuroblastoma (NB) is a serious tumor linked to neural crest cells, with MYCN gene amplification and certain chromosome alterations generally indicating a worse prognosis for patients.
- - This study utilized digital droplet PCR to effectively detect MYCN amplification and chromosome 11q copy number alterations (CNA) in NB samples, comparing results with more traditional SNP chip arrays to ensure accuracy.
- - Digital droplet PCR provides a faster and practical alternative to methods like FISH and Southern blotting for identifying CNAs in neuroblastoma, which can aid in timely risk assessment after diagnosis.
The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations.
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- The study aimed to understand the molecular causes of pediatric germ cell tumors (GCTs) using various genomic analysis techniques on 51 tumor samples from both genders and different age groups.
- Findings revealed that germinomas and embryonal carcinomas exhibited high levels of pluripotent gene expression, while yolk sac tumors showed signs of endodermal gene overexpression.
- Researchers suggest potential treatment targets based on gene expression patterns: KIT for germinomas, TNFRSF8 for embryonal carcinomas, and ERBB4 for yolk sac tumors.
Article Synopsis
- Hepatoblastoma is the most common liver cancer in children, but its genetic makeup and treatment targets are not fully understood.
- A study analyzed 59 hepatoblastoma samples using various techniques and identified three distinct clusters based on DNA methylation patterns, which relate to different clinical outcomes.
- The findings suggest specific genetic characteristics linked to poorer outcomes in certain clusters and highlight potential new treatment strategies that could improve responses to therapy in high-risk patients.
Spliceosome mutations are frequently found in myelodysplasia. Splicing alterations induced by these mutations, their precise targets, and the effect at the transcript level have not been fully elucidated. Here we report transcriptomic analyses of 265 bone marrow samples from myelodysplasia patients, followed by a validation using CRISPR/Cas9-mediated gene editing and an assessment of nonsense-mediated decay susceptibility.
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- Inherited bone-marrow-failure syndromes (IBMFSs) are a group of genetic disorders linked to bone marrow failure, congenital issues, and a higher cancer risk, with p53 activation thought to play a key role in their development.
- Recent findings revealed specific mutations in the TP53 gene in two patients exhibiting symptoms like low antibody levels, growth delays, and small head size, which resemble conditions such as Diamond-Blackfan anemia and dyskeratosis congenita.
- Interestingly, these mutations led to a loss of part of the p53 protein but resulted in increased transcriptional activity, which was unusual; further experiments in zebrafish and stem cells showed disrupted red blood cell production, highlighting a new connection between p
Article Synopsis
- The study focuses on the chromosomal translocation t(8;21), which creates the oncogenic RUNX1-RUNX1T1 fusion and is found in about 10% of acute myelogenous leukemia (AML) cases.
- By performing whole and targeted exome sequencing, researchers identified frequent truncating mutations alongside recurrent mutations in a specific subtype of AML.
- The investigation into ASXL2, using a mouse model lacking this gene, demonstrated that its deficiency leads to significant hematopoietic problems, including myeloid hyperplasia and cell differentiation issues, highlighting ASXL2's importance in normal blood cell development.
HLA-DPB1 T-cell epitope (TCE) mismatching algorithm and rs9277534 SNP at the 3' untranslated region (3'UTR) in the HLA-DPB1 gene are key factors for transplant-related events in unrelated hematopoietic cell transplantation (UR-HCT). However, the association of these 2 mechanisms has not been elucidated. We analyzed 19 frequent HLA-DPB1 alleles derived from Japanese healthy subjects by next-generation sequencing of the entire HLA-DPB1 gene region and multi-SNP data of the HLA region in 1589 UR-HCT pairs.
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