P-053 Characterization of 305 patients with myelodysplastic syndromes and 20q-deletion: Cytomorphological features, and concomitant cytogenetic and molecular genetic alterations

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.

Download Full-text

Implication of the Molecular Characterization of Acute Myeloid Leukemia

Hematology ◽

10.1182/asheducation-2007.1.412 ◽

2007 ◽

Vol 2007 (1) ◽

pp. 412-419 ◽

Cited By ~ 23

Author(s):

Hartmut Döhner

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Molecular Genetic ◽

Gene Mutations ◽

Genetic Alterations ◽

Molecular Alterations ◽

Binding Factor ◽

Molecular Therapies ◽

Acute Myeloid

AbstractThe identification of molecular genetic alterations such as gene mutations or deregulated gene expression in acute myeloid leukemia (AML) has greatly advanced our understanding of leukemogenesis. These markers now allow us to unravel the enormous heterogeneity seen within cytogenetically defined subgroups of AML. Furthermore, the molecular alterations are providing targets for molecular therapies. In this article, major molecular findings of prognostic and predictive significance are reviewed, with an emphasis on the discussion of gene mutations found in two major AML subgroups, cytogenetically normal and core-binding factor AML.

Download Full-text

Molecular genetic markers for thyroid FNAB

Nuklearmedizin ◽

10.1055/s-0037-1616610 ◽

2015 ◽

Vol 54 (03) ◽

pp. 94-100 ◽

Cited By ~ 4

Author(s):

P. B. Musholt ◽

T. J. Musholt

Keyword(s):

Genetic Markers ◽

Thyroid Nodules ◽

Molecular Genetic ◽

Genetic Alterations ◽

Diagnostic Tools ◽

Ultrasound Screening ◽

Thyroid Malignancy ◽

Thyroid Carcinomas ◽

Molecular Genetic Markers ◽

The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

Download Full-text

Detection and Characterization of Genetic Alterations on Chromosome 16 for Breast Cancer.

10.21236/ada310545 ◽

1996 ◽

Author(s):

Rosemary B. Duda

Keyword(s):

Breast Cancer ◽

Genetic Alterations ◽

Chromosome 16

Download Full-text

Characterization of Genetic Alterations in Ovarian Cancer

10.21236/ada421954 ◽

2003 ◽

Author(s):

David I. Smith

Keyword(s):

Ovarian Cancer ◽

Genetic Alterations

Download Full-text

Altered Spatial Composition of the Immune Cell Repertoire in Association to CD34+ Blasts in Myelodysplastic Syndromes and Secondary Acute Myeloid Leukemia

Cancers ◽

10.3390/cancers13020186 ◽

2021 ◽

Vol 13 (2) ◽

pp. 186

Author(s):

Marcus Bauer ◽

Christoforos Vaxevanis ◽

Haifa Kathrin Al-Ali ◽

Nadja Jaekel ◽

Christin Le Hoa Naumann ◽

...

Keyword(s):

T Cells ◽

Acute Myeloid Leukemia ◽

Myelodysplastic Syndromes ◽

Myeloid Leukemia ◽

Multispectral Imaging ◽

Immune Cell ◽

Genetic Alterations ◽

Spatial Proximity ◽

Secondary Acute Myeloid Leukemia ◽

Acute Myeloid

Background: Myelodysplastic syndromes (MDS) are caused by a stem cell failure and often include a dysfunction of the immune system. However, the relationship between spatial immune cell distribution within the bone marrow (BM), in relation to genetic features and the course of disease has not been analyzed in detail. Methods: Histotopography of immune cell subpopulations and their spatial distribution to CD34+ hematopoietic cells was determined by multispectral imaging (MSI) in 147 BM biopsies (BMB) from patients with MDS, secondary acute myeloid leukemia (sAML), and controls. Results: In MDS and sAML samples, a high inter-tumoral immune cell heterogeneity in spatial proximity to CD34+ blasts was found that was independent of genetic alterations, but correlated to blast counts. In controls, no CD8+ and FOXP3+ T cells and only single MUM1p+ B/plasma cells were detected in an area of ≤10 μm to CD34+ HSPC. Conclusions: CD8+ and FOXP3+ T cells are regularly seen in the 10 μm area around CD34+ blasts in MDS/sAML regardless of the course of the disease but lack in the surrounding of CD34+ HSPC in control samples. In addition, the frequencies of immune cell subsets in MDS and sAML BMB differ when compared to control BMB providing novel insights in immune deregulation.

Download Full-text

Copy Number Variation and Rearrangements Assessment in Cancer: Comparison of Droplet Digital PCR with the Current Approaches

International Journal of Molecular Sciences ◽

10.3390/ijms22094732 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4732

Author(s):

Vincenza Ylenia Cusenza ◽

Alessandra Bisagni ◽

Monia Rinaldini ◽

Chiara Cattani ◽

Raffaele Frazzi

Keyword(s):

Digital Pcr ◽

Genetic Alterations ◽

Droplet Digital Pcr ◽

Molecular Oncology ◽

Therapeutic Choice ◽

Golden Standard ◽

Number Variation ◽

Key Aspects

The cytogenetic and molecular assessment of deletions, amplifications and rearrangements are key aspects in the diagnosis and therapy of cancer. Not only the initial evaluation and classification of the disease, but also the follow-up of the tumor rely on these laboratory approaches. The therapeutic choice can be guided by the results of the laboratory testing. Genetic deletions and/or amplifications directly affect the susceptibility or the resistance to specific therapies. In an era of personalized medicine, the correct and reliable molecular characterization of the disease, also during the therapeutic path, acquires a pivotal role. Molecular assays like multiplex ligation-dependent probe amplification and droplet digital PCR represent exceptional tools for a sensitive and reliable detection of genetic alterations and deserve a role in molecular oncology. In this manuscript we provide a technical comparison of these two approaches with the golden standard represented by fluorescence in situ hybridization. We also describe some relevant targets currently evaluated with these techniques in solid and hematologic tumors.

Download Full-text

Graphene, an Interesting Nanocarbon Allotrope for Biosensing Applications: Advances, Insights, and Prospects

Biomedical Engineering and Computational Biology ◽

10.1177/1179597220983821 ◽

2021 ◽

Vol 12 ◽

pp. 117959722098382

Author(s):

Farid Menaa ◽

Yazdian Fatemeh ◽

Sandeep K Vashist ◽

Haroon Iqbal ◽

Olga N Sharts ◽

...

Keyword(s):

Cost Effective ◽

Genetic Alterations ◽

Multiplex Detection ◽

Quantitative Characterization ◽

Disease Biomarkers ◽

Qualitative And Quantitative ◽

Sensing Systems ◽

Doped Graphene ◽

Bioanalytical Applications

Graphene, a relatively new two-dimensional (2D) nanomaterial, possesses unique structure (e.g. lighter, harder, and more flexible than steel) and tunable physicochemical (e.g. electronical, optical) properties with potentially wide eco-friendly and cost-effective usage in biosensing. Furthermore, graphene-related nanomaterials (e.g. graphene oxide, doped graphene, carbon nanotubes) have inculcated tremendous interest among scientists and industrials for the development of innovative biosensing platforms, such as arrays, sequencers and other nanooptical/biophotonic sensing systems (e.g. FET, FRET, CRET, GERS). Indeed, combinatorial functionalization approaches are constantly improving the overall properties of graphene, such as its sensitivity, stability, specificity, selectivity, and response for potential bioanalytical applications. These include real-time multiplex detection, tracking, qualitative, and quantitative characterization of molecules (i.e. analytes [H2O2, urea, nitrite, ATP or NADH]; ions [Hg2+, Pb2+, or Cu2+]; biomolecules (DNA, iRNA, peptides, proteins, vitamins or glucose; disease biomarkers such as genetic alterations in BRCA1, p53) and cells (cancer cells, stem cells, bacteria, or viruses). However, there is still a paucity of comparative reports that critically evaluate the relative toxicity of carbon nanoallotropes in humans. This manuscript comprehensively reviews the biosensing applications of graphene and its derivatives (i.e. GO and rGO). Prospects and challenges are also introduced.

Download Full-text