ALK evaluation in the world of multiplex testing: Network Genomic Medicine (NGM): the Cologne model for implementing personalised oncology

Heydt, Carina; Kostenko, Anna; Merkelbach‐Bruse, Sabine; Wolf, Juergen; Büttner, Reinhard

doi:10.1093/annonc/mdw303

Cited by 28 publications

(21 citation statements)

References 43 publications

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“…Reliable ISH assays are commercially available and most often include a so-called "break-apart" probe design, in which 2 differentially labeled probes hybridize adjacent to the known break points of the main fusion genes (eg, ALK, ROS1, the NTRKs, or RET) and are separated by the translocation event. 15 Whereas in normal cells, 2 fusion signals can be detected, tumor cells show break-apart signal patterns with separate signals of each probe in addition to a fusion signal. For the assessment of a positive fusion event, several recommendations have been established.…”

Section: Cancer Cytopathology September 2020mentioning

confidence: 99%

“…11,12 Several algorithms for fusion diagnostics in a clinical setting have been suggested, all of which include parallel sequencing as a last resort. 15,42,69…”

Section: Ihcmentioning

confidence: 99%

“…At the same time, access to clinical trials should be possible. 15 In recent years, more than 190 network partner sites all over Germany sent patient material for analysis.…”

Section: Network For Molecular Pathology Diagnosticsmentioning

confidence: 99%

“…For this purpose, the Network Genomic Medicine (NGM) established the model of central comprehensive molecular testing and delivery of decentralized consultation and therapy for patients. 15 In 2018, the German Cancer Aid (DKH) rolled out this interdisciplinary health care model to all German comprehensive cancer centers currently funded by the DKH. 16 To provide both patients and clinicians with accurate diagnosis, external quality assessment (EQA) is gaining more and more importance.…”

Section: Introductionmentioning

confidence: 99%

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Predictive molecular pathology of lung cancer in Germany with focus on gene fusion testing: Methods and quality assurance

Siemanowski

Heydt

Merkelbach‐Bruse

2020

Cancer Cytopathology

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Predictive molecular testing has become an important part of the diagnosis of any patient with lung cancer. Using reliable methods to ensure timely and accurate results is inevitable for guiding treatment decisions. In the past few years, parallel sequencing has been established for mutation testing, and its use is currently broadened for the detection of other genetic alterations, such as gene fusion and copy number variations. In addition, conventional methods such as immunohistochemistry and in situ hybridization are still being used, either for formalin‐fixed, paraffin‐embedded tissue or for cytological specimens. For the development and broad implementation of such complex technologies, interdisciplinary and regional networks are needed. The Network Genomic Medicine (NGM) has served as a model of centralized testing and decentralized treatment of patients and incorporates all German comprehensive cancer centers. Internal quality control, laboratory accreditation, and participation in external quality assessment is mandatory for the delivery of reliable results. Here, we provide a summary of current technologies used to identify patients who have lung cancer with gene fusions, briefly describe the structures of NGM and the national NGM (nNGM), and provide recommendations for quality assurance.

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Section: Cancer Cytopathology September 2020mentioning

confidence: 99%

“…11,12 Several algorithms for fusion diagnostics in a clinical setting have been suggested, all of which include parallel sequencing as a last resort. 15,42,69…”

Section: Ihcmentioning

confidence: 99%

“…At the same time, access to clinical trials should be possible. 15 In recent years, more than 190 network partner sites all over Germany sent patient material for analysis.…”

Section: Network For Molecular Pathology Diagnosticsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Predictive molecular pathology of lung cancer in Germany with focus on gene fusion testing: Methods and quality assurance

Siemanowski

Heydt

Merkelbach‐Bruse

2020

Cancer Cytopathology

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“…This has led to a significant improvement in the outcome for HER2+ breast and gastric cancer [13][14][15][16][17][18] . Other examples of approved biomarkers in solid tumor targeted drug therapy are hormone receptor status in gynecologic and prostate cancer, RAS, EGFR, and ALK in lung and colorectal cancer [19][20][21]. Erlotinib is applied to patients with an EGFR mutation and a BRAF mutation indicates the clinical efficacy of BRAF inhibitors, such as vemurafenib and dabrafenib for melanoma patients [22][23][24].…”

mentioning

confidence: 99%

Bringing 3D tumor models to the clinic – predictive value for personalized medicine

Halfter¹,

Mayer

2017

Biotechnology Journal

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Current decision-guiding algorithms in cancer drug treatment are based on decades of research and numerous clinical trials. For the majority of patients, this data is successfully applied for a systemic disease management. For a number of patients however, treatment stratification according to clinically based risk criteria will not be sufficient. The most effective treatment options are ideally identified prior to the start of clinical drug therapy. This review will discuss the implementation of three-dimensional (3D) cell culture models as a preclinical testing paradigm for the efficacy of clinical cancer treatment. Patient tumor-derived cells in 3D cultures duplicate the individual tumor microenvironment with a minimum of confounding factors. Clinical implementation of such personalized tumor models requires a high quality of methodological and clinical validation comparable to other biomarkers. A non-systematic literature search demonstrated the small number of prospective studies that have been conducted in this area of research. This may explain the current reluctance of many physicians and insurance providers in implementing this type of assay into the clinical diagnostic routine despite potential benefit for patients. Achieving valid and reproducible results with a high level of evidence is central in improving the acceptance of preclinical 3D tumor models.

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Genetic instability and recurrent MYC amplification in ALK‐translocated NSCLC: a central role of TP53 mutations

Alidousty

Baar

Martelotto

et al. 2018

The Journal of Pathology

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The anaplastic lymphoma kinase (ALK) rearrangement defines a distinct molecular subtype of non‐small cell lung cancer (NSCLC). Despite the excellent initial efficacy of ALK inhibitors in patients with ALK+ lung cancer, resistance occurs almost inevitably. To date, there is no reliable biomarker allowing the identification of patients at higher risk of relapse. Here, we analysed a subset of 53 ALK+ tumours with and without TP53 mutation and ALK+ NSCLC cell lines by NanoString nCounter technology. We found that the co‐occurrence of early TP53 mutations in ALK+ NSCLC can lead to chromosomal instability: 24% of TP53‐mutated patients showed amplifications of known cancer genes such as MYC (14%), CCND1 (10%), TERT (5%), BIRC2 (5%), ORAOV1 (5%), and YAP1 (5%). MYC‐overexpressing ALK+ TP53‐mutated cells had a proliferative advantage compared to wild‐type cells. ChIP‐Seq data revealed MYC‐binding sites within the promoter region of EML4, and MYC overexpression in ALK+ TP53‐mutated cells resulted in an upregulation of EML4–ALK, indicating a potential MYC‐dependent resistance mechanism in patients with increased MYC copy number. Our study reveals that ALK+ NSCLC represents a more heterogeneous subgroup of tumours than initially thought, and that TP53 mutations in that particular cancer type define a subset of tumours that harbour chromosomal instability, leading to the co‐occurrence of pathogenic aberrations. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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ALK evaluation in the world of multiplex testing: Network Genomic Medicine (NGM): the Cologne model for implementing personalised oncology

Cited by 28 publications

References 43 publications

Predictive molecular pathology of lung cancer in Germany with focus on gene fusion testing: Methods and quality assurance

Predictive molecular pathology of lung cancer in Germany with focus on gene fusion testing: Methods and quality assurance

Bringing 3D tumor models to the clinic – predictive value for personalized medicine

Genetic instability and recurrent MYC amplification in ALK‐translocated NSCLC: a central role of TP53 mutations

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