X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Oxford University Press (OUP)  (4)
  • Ichimura, Koichi  (4)
  • 1
    Online Resource
    Online Resource
    GEN-13 PAIRED MUTATIONAL ANALYSIS IN SECONDARY NERVOUS SYSTEM LYMPHOMA AND PCNSL SYSTEMIC RELAPSE REVEALS DRIVER MUTATION CANDIDATES IN THE CENTRAL NERVOUS SYSTEM
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Advances Vol. 4, No. Supplement_3 ( 2022-12-03), p. iii4-iii4
    Details
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 4, No. Supplement_3 ( 2022-12-03), p. iii4-iii4
    Abstract: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma confined to the brain, eyes, and the spinal cord. The mechanism of central nervous system (CNS) tropism in PCNSL has not been fully elucidated. Diffuse large B cell lymphomas (DLBCLs) occasionally present with distant recurrence, which can involve inside and outside the CNS. Secondary central nervous system lymphomas (SCNSLs) are CNS relapse of systemic lymphoma. PCNSLs also rarely present with systemic relapse. We have previously reported in our study of whole exome sequencing that PCNSLs harbor frequent mutations in genes of B cell receptor pathway members and aberrant somatic hypermutation (aSHM) target genes. Although several genetic alterations were identified as more frequent in PCNSLs compared with systemic lymphomas, specific genetic alterations which serve as the driver for CNS tropism in PCNSLs has not been identified. In order to search for mutations which might serve as driver mutations in the CNS, we have performed targeted sequencing in paired samples from patients with recurrent lymphomas, either SCNSLs or PCNSL systemic relapses, using Ion Torrent multiplex PCR. Mutational profiles were compared between the primary and recurrent tumor. Six cases (four SCNSL cases and two PCNSL systemic relapse cases) were analyzed. Of note, in the SCNSL cases, several de novo mutations were enriched only among the recurrent CNS tumors. Among these mutations, BTG2 mutations were observed in 3/4 (75%), and B2M and KLHL14 mutations were observed in 2/4 (50%) cases. In the two PCNSL systemic relapse cases, KMT2D mutations were enriched only in the recurrent systemic tumors. It is suggested that these de novo mutations in the recurrent CNS tumors might serve as driver mutations in the CNS. Further analysis in larger cohorts, and functional studies are required in order to validate these findings.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    URL: Article
    DOI: 10.1093/noajnl/vdac167.014
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 3009682-0
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 2
    Online Resource
    Online Resource
    ML-7 Liquid biopsy for MYD88 mutation in cerebrospinal fluid in patients with suspected primary CNS lymphoma
    Oxford University Press (OUP) ; 2021
    In:  Neuro-Oncology Advances Vol. 3, No. Supplement_6 ( 2021-12-06), p. vi23-vi23
    Details
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 3, No. Supplement_6 ( 2021-12-06), p. vi23-vi23
    Abstract: Background: Treatment intervention for central nervous system lymphoma (CNSL) requires pathological diagnosis by surgical biopsy. However, there are some cases in which the risk of surgery is high due to age, comorbidities, localization of lesions, etc. We are developing a CNSL diagnostic method based on the detection of MYD88 L265P mutation by digital PCR (dPCR) using CSF-DNA, and a high accuracy with a sensitivity of 92.9% and a specificity of 100% has been reported. Here, we report two cases with suspected brain stem CNSL, whose treatment strategy was determined by integrated clinico-laboratory information including neurological presentations, imaging, and the result of liquid biopsy. Result: Case 1. A 63-year-old woman visited our hospital with a complaint of right hemiplegia, which deteriorated in two months. MR images revealed a contrast-enhancing lesion in the left midbrain-ventral pons, suggesting CNSL. Biopsy was not considered because of its location, while dPCR using CSF-DNA showed a cluster of MYD88 mutation signals. Based on these work-ups, she was treated with high-dose methotrexate-based chemotherapy, resulting in a complete response with marked improvement of symptoms. Case 2. An 83-year-old man was referred for a history of diplopia and ataxic gait lasting for a month. MR images revealed an invasive lesion on his right midbrain-dorsal pons. Biopsy was declined due to the location, and liquid biopsy using CSF-DNA was performed to assist the diagnosis. In the first test, the CSF-DNA yield was too insufficient to determine the mutation signal by dPCR. The second dPCR using sufficient amount of CSF-DNA resulted in the Target/Total value of 0.049% which was lower than the threshold, suggesting the absence of MYD88 mutation. The patient underwent radiation therapy accordingly.Conclusions: CSF MYD88 mutation analysis by dPCR may have clinical utility and requires sufficient amount of CSF-DNA for exclusion of noise signals.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    URL: Article
    DOI: 10.1093/noajnl/vdab159.088
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 3009682-0
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 3
    Online Resource
    Online Resource
    GCT-34. ELUCIDATION OF THE MECHANISMS OF TUMORIGENESIS IN INTRACRANIAL GERM CELL TUMOR BY WHOLE GENOME SEQUENCE
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii334-iii335
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii334-iii335
    Abstract: Intracranial germ cell tumors (iGCT) are heterogenous group of primary brain tumors that consist of various subtype, and driver genetic alterations in iGCTs remain largely unknown. We have previously reported in a study of whole exome sequence that iGCTs frequently harbored mutations in the KIT gene and its downstream MAPK/PI3K pathway, regardless of tumor subtype. However, no mutations were detected in about one-quarter of germinomas and half of non-germinomatous germ cell tumors. A genome-wide methylation profiling revealed that only germinomas exhibited extreme DNA hypomethylation among iGCTs. Moreover, in mixed iGCT tumors which contained more than one tumor subtypes, each component exhibited distinct methylation status depending on the subtype, while they shared the same mutations. These data suggested that not only mutations in the coding region as previously reported, but also genetic alterations in regulatory regions including promoters and enhancers as well as non-coding RNA genes may be involved in the tumorigenesis of iGCTs. In order to comprehensively search for driver gene alterations, we performed whole genome sequence in 18 paired tumor blood samples from iGCT tumors (16germinomas and two yolk sac tumors (YST)) registered in the Intracranial Germ Cell Tumor Genome Analysis Consortium. In a preliminary analysis of four cases, YSTs harbored a significantly higher number of structural abnormalities, compared with germinomas. Of note, 62 structural abnormalities were clustered within the small genomic region of 95Mb at 1q21-44 in one YST case, suggesting a possibility of chromothripsis. A full analysis of somatic alterations is underway and will be reported.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa222.253
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
  • 4
    Online Resource
    Online Resource
    ML-06 Diagnostic value of liquid biopsy for CNS lymphoma by detection of specific gene mutations in the cerebrospinal fluid
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Advances Vol. 2, No. Supplement_3 ( 2020-11-28), p. ii16-ii16
    Details
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 2, No. Supplement_3 ( 2020-11-28), p. ii16-ii16
    Abstract: Backgrounds & Purpose: Central nervous system lymphoma (CNSL) is the second most common primary malignant brain tumor. Brain biopsy is indispensable to confirm the diagnosis of CNSL, but has a potential risk of inducing hemorrhagic complications in the brain. Therefore, liquid biopsy using the cerebrospinal fluid (CSF) has attracted an attention as a less invasive diagnostic method. In this study, we established a digital PCR-based method to detect MYD88 mutations in CSF and evaluated its efficacy. Methods: Matched CSF and biopsy samples from CNSL patients collected before the start of chemotherapy were used. Cellular DNA and cell free DNA (cfDNA) of CSF were separately extracted from the pellet and the supernatant fraction of CSF, respectively. Presence of the MYD88 L265P mutation was examined in each fraction by the digital PCR. The mutational status obtained by liquid biopsy was compared with that of the matched biopsy specimen examined by pyrosequencing. Result: A total of 36 paired samples were used. When the cutoff value of Target/Total ratio was 0.25%, sensitivity, specificity, and area under the curve (AUC) of the digital PCR detection using cellular DNA were 92.9%, 100%, and 0.95, respectively, while they were 100%, 100%, and 1.00 using cfDNA. Conclusion: We showed that the digital PCR method was highly sensitive and specific in detecting MYD88 mutations in the CSF. We propose that CSF liquid biopsy may serve a clinically applicable surrogate to make a diagnosis of CNSL.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    URL: Article
    DOI: 10.1093/noajnl/vdaa143.069
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 3009682-0
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Online Resource
    Open Access Request
    Availability (electronic / print)
Nothing or not found what you are looking for? Please check your search query or use the Interlibrary Loan Search.
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages