GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Distinct Mutation Patterns Reveal Melanoma Subtypes and Influence Immunotherapy Response in Advanced Melanoma Patients
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 9 ( 2020-08-20), p. 2359-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 9 ( 2020-08-20), p. 2359-
    Abstract: The detection of somatic driver mutations by next-generation sequencing (NGS) is becoming increasingly important in the care of advanced melanoma patients. In our study, we evaluated the NGS results of 82 melanoma patients from clinical routine in 2017. Besides determining the tumor mutational burden (TMB) and annotation of all genetic driver alterations, we investigated their potential as a predictor for resistance to immune checkpoint inhibitors (ICI) and as a distinguishing feature between melanoma subtypes. Melanomas of unknown primary had a similar mutation pattern and TMB to cutaneous melanoma, which hints at its cutaneous origin. Besides the typical hotspot mutation in BRAF and NRAS, we frequently observed CDKN2A deletions. Acral and mucosal melanomas were dominated by CNV alterations affecting PDGFRA, KIT, CDK4, RICTOR, CCND2 and CHEK2. Uveal melanoma often had somatic SNVs in GNA11/Q and amplification of MYC in all cases. A significantly higher incidence of BRAF V600 mutations and EGFR amplifications, PTEN and TP53 deletions was found in patients with disease progression while on ICI. Thus, NGS might help to characterize melanoma subtypes more precisely and to identify possible resistance mechanisms to ICI therapy. Nevertheless, NGS based studies, including larger cohorts, are needed to support potential genetic ICI resistance mechanisms.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12092359
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Multiparametric Classification of Non-Muscle Invasive Papillary Urothelial Neoplasms: Combining Morphological, Phenotypical, and Molecular Features for Improved Risk Stratification
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 15 ( 2022-07-23), p. 8133-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 15 ( 2022-07-23), p. 8133-
    Abstract: Diagnosis and grading of non-invasive papillary urothelial tumors according to the current WHO classification poses some challenges for pathologists. The diagnostic reproducibility of separating low-grade and high-grade lesions is low, which impacts their clinical management. Whereas papillary urothelial neoplasms with low malignant potential (PUN-LMP) and low-grade papillary non-invasive carcinoma (LG-PUC) are comparable and show frequent local recurrence but rarely metastasize, high-grade papillary non-invasive carcinoma (HG-PUC) has a poor prognosis. The main objective of this work is to develop a multiparametric classification to unambiguously distinguish low-grade and high-grade tumors, considering immunohistochemical stains for p53, FGFR3, CK20, MIB-1, p16, p21 and p-HH3, and pathogenic mutations in TP53, FGFR3, TP53, ERCC2, PIK3CA, PTEN and STAG2. We reviewed and analyzed the clinical and histological data of 45 patients with a consensus diagnosis of PUN-LMP (n = 8), non-invasive LG-PUC (n = 23), and HG-PUC (n = 14). The proliferation index and mitotic count assessed with MIB-1 and P-HH3 staining, respectively correlated with grading and clinical behavior. Targeted sequencing confirmed frequent FGFR3 mutations in non-invasive papillary tumors and identified mutations in TP53 as high-risk. Cluster analysis of the different immunohistochemical and molecular parameters allowed a clear separation in two different clusters: cluster 1 corresponding to PUN-LMP and LG-PUC (low MIB-1 and mitotic count/FGFR3 and STAG2 mutations) and cluster 2, HG-PUC (high MIB-1 and mitosis count/CK20 +++ expression, FGFR3 WT and TP53 mutation). Further analysis is required to validate and analyze the reproducibility of these clusters and their biological and clinical implication.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23158133
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Molecular Progression of Myeloproliferative and Myelodysplastic/Myeloproliferative Neoplasms: A Study on Sequential Bone Marrow Biopsies
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 22 ( 2021-11-09), p. 5605-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 22 ( 2021-11-09), p. 5605-
    Abstract: Myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) both harbor the potential to undergo myelodysplastic progression or acceleration and can transform into blast-phase MPN or MDS/MPN, a form of secondary acute myeloid leukemia (AML). Although the initiating transforming events are yet to be determined, current concepts suggest a stepwise acquisition of (additional) somatic mutations—apart from the initial driver mutations—that trigger disease evolution. In this study we molecularly analyzed paired bone marrow samples of MPN and MDS/MPN patients with known progression and compared them to a control cohort of patients with stable disease course. Cases with progression displayed from the very beginning a higher number of mutations compared to stable ones, of which mutations in five (ASXL1, DNMT3A, NRAS, SRSF2 and TP53) strongly correlated with progression and/or transformation, even if only one of these genes was mutated, and this particularly applied to MPN. TET2 mutations were found to have a higher allelic frequency than the putative driver mutation in three progressing cases (“TET2-first”), whereas two stable cases displayed a TET2-positive subclone (“TET2-second”), supporting the hypothesis that not only the sum of mutations but also their order of appearance matters in the course of disease. Our data emphasize the importance of genetic testing in MPN and MDS/MPN patients in terms of risk stratification and identification of imminent disease progression.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13225605
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    The Pathological Spectrum of Systemic Anaplastic Large Cell Lymphoma (ALCL)
    MDPI AG ; 2018
    In:  Cancers Vol. 10, No. 4 ( 2018-04-04), p. 107-
    Details
    In: Cancers, MDPI AG, Vol. 10, No. 4 ( 2018-04-04), p. 107-
    Abstract: Anaplastic large cell lymphoma (ALCL) represents a group of malignant T-cell lymphoproliferations that share morphological and immunophenotypical features, namely strong CD30 expression and variable loss of T-cell markers, but differ in clinical presentation and prognosis. The recognition of anaplastic lymphoma kinase (ALK) fusion proteins as a result of chromosomal translocations or inversions was the starting point for the distinction of different subgroups of ALCL. According to their distinct clinical settings and molecular findings, the 2016 revised World Health Organization (WHO) classification recognizes four different entities: systemic ALK-positive ALCL (ALK+ ALCL), systemic ALK-negative ALCL (ALK− ALCL), primary cutaneous ALCL (pC-ALCL), and breast implant-associated ALCL (BI-ALCL), the latter included as a provisional entity. ALK is rearranged in approximately 80% of systemic ALCL cases with one of its partner genes, most commonly NPM1, and is associated with favorable prognosis, whereas systemic ALK− ALCL shows heterogeneous clinical, phenotypical, and genetic features, underlining the different oncogenesis between these two entities. Recognition of the pathological spectrum of ALCL is crucial to understand its pathogenesis and its boundaries with other entities. In this review, we will focus on the morphological, immunophenotypical, and molecular features of systemic ALK+ and ALK− ALCL. In addition, BI-ALCL will be discussed.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers10040107
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Influence of Biopsy Technique on Molecular Genetic Tumor Characterization in Non-Small Cell Lung Cancer—The Prospective, Randomized, Single-Blinded, Multicenter PROFILER Study Protocol
    MDPI AG ; 2020
    In:  Diagnostics Vol. 10, No. 7 ( 2020-07-06), p. 459-
    Details
    In: Diagnostics, MDPI AG, Vol. 10, No. 7 ( 2020-07-06), p. 459-
    Abstract: The detection of molecular alterations is crucial for the individualized treatment of advanced non-small cell lung cancer (NSCLC). Missing targetable alterations may have a major impact on patient’s progression free and overall survival. Although laboratory testing for molecular alterations has continued to improve; little is known about how biopsy technique affects the detection rate of different mutations. In the retrospective study detection rate of epidermal growth factor (EGFR) mutations in tissue extracted by bronchoscopic cryobiopsy (CB was significantly higher compared to other standard biopsy techniques. This prospective, randomized, multicenter, single blinded study evaluates the accuracy of molecular genetic characterization of NSCLC for different cell sampling techniques. Key inclusion criteria are suspected lung cancer or the suspected relapse of known NSCLC that is bronchoscopically visible. Patients will be randomized, either to have a CB or a bronchoscopic forceps biopsy (FB). If indicated, a transbronchial needle aspiration (TBNA) of suspect lymph nodes will be performed. Blood liquid biopsy will be taken before tissue biopsy. The primary endpoint is the detection rate of molecular genetic alterations in NSCLC, using CB and FB. Secondary endpoints are differences in the combined detection of molecular genetic alterations between FB and CB, TBNA and liquid biopsy. This trial plans to recruit 540 patients, with 178 evaluable patients per study cohort. A histopathological and molecular genetic evaluation will be performed by the affiliated pathology departments of the national network for genomic medicine in lung cancer (nNGM), Germany. We will compare the diagnostic value of solid tumor tissue, lymph node cells and liquid biopsy for the molecular genetic characterization of NSCLC. This reflects a real world clinical setting, with potential direct impact on both treatment and survival.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics10070459
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662336-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 3 ( 2020-02-26), p. 540-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 3 ( 2020-02-26), p. 540-
    Abstract: Background: Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. MDM2/4 as well as EGFR amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to MDM2/4 or EGFR amplifications and melanoma type. Methods: We conducted a query of our melanoma registry, looking for patients with metastatic acral or mucosal melanoma treated by ICI. Whole exome sequencing, FISH and immunohistochemistry on melanoma tissue could be performed on 45 of the total cohort of 51 patients. Data were correlated with patients’ responses to ICI and survival. Results: 22 out of 51 patients had hyperprogressive disease (an increase in tumor load of 〉 50% at the first staging). Hyperprogression occurred more often in case of MDM2/4 or EGFR amplification or 〈 1% PD-L1 positive tumor cells. Nevertheless, this association was not significant. Interestingly, the anorectal melanoma type and the presence of liver metastases were significantly associated with worse survival. Conclusions: So far, we found no reliable predictive marker for patients who develop hyperprogression on ICI, specifically with regard to MDM2/4 or EGFR amplifications. Nevertheless, patients with anorectal melanoma, liver metastases or melanoma with amplified MYC seem to have an increased risk of not benefitting from ICI.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12030540
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...