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A combined gene exp...
A combined gene expression tool for parallel histological prediction and gene fusion detection in non-small cell lung cancer
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- Karlsson, Anna (författare)
- Lund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Research Group Lung Cancer,Lund University Research Groups
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- Cirenajwis, Helena (författare)
- Lund University,Lunds universitet,Melanoma Genomics,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Ericson-Lindquist, Kajsa (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Regional Laboratories Region Skåne
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- Brunnström, Hans (författare)
- Lund University,Lunds universitet,Förbättrad diagnostik och prognostik vid lungcancer och metastaser till lunga,Forskargrupper vid Lunds universitet,Improved diagnostics and prognostics of lung cancer and metastases to the lungs,Lund University Research Groups,Regional Laboratories Region Skåne
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- Reuterswärd, Christel (författare)
- Lund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Research Group Lung Cancer,Lund University Research Groups
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- Jönsson, Mats (författare)
- Lund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Research Group Lung Cancer,Lund University Research Groups
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- Ortiz-Villalon, Cristian (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden,Karolinska University Hospital
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- Hussein, Aziz (författare)
- Sahlgrens Univ Hosp, Dept Pathol & Cytol, Gothenburg, Sweden,Department of Pathology and cytology, Sahlgrenska university hospital, Gothenburg, Sweden
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- Bergman, Bengt (författare)
- Sahlgrens Univ Hosp, Dept Resp Med, Gothenburg, Sweden,Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
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- Vikström, Anders, 1955- (författare)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Medicinska fakulteten,Region Östergötland, Lungmedicinska kliniken US,Univ Hosp Linkoping, Dept Pulm Med, Linkoping, Sweden,Linköping University Hospital
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- Monsef, Nastaran, 1973- (författare)
- Linköping University,Linköpings universitet,Avdelning för neurobiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi,Linkoping Univ, Dept Pathol, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden
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- Brandén, Eva (författare)
- Uppsala University,Karolinska Institute,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Karolinska Inst, Dept Med Solna & CMM, Resp Med Unit, Stockholm, Sweden;Karolinska Univ Hosp Solna, Stockholm, Sweden,Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden; Centre for Research and Development, Uppsala University; Region Gävleborg, Gävle, Sweden
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- Koyi, Hirsh (författare)
- Uppsala University,Karolinska Institute,Karolinska Institutet,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Karolinska Inst, Dept Med Solna & CMM, Resp Med Unit, Stockholm, Sweden;Karolinska Univ Hosp Solna, Stockholm, Sweden,Respiratory Medicine Unit, Department of Medicine Solna and CMM, Karolinska Institutet and Karolinska University Hospital Solna, Stockholm, Sweden; Centre for Research and Development, Uppsala University; Region Gävleborg, Gävle, Sweden
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- de Petris, Luigi (författare)
- Karolinska Institute,Karolinska Institutet,Karolinska Univ Hosp, Thorac Oncol Unit, Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden,Karolinska University Hospital
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- Micke, Patrick (författare)
- Uppsala University,Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke,Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
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- Patthey, Annika (författare)
- Umea Univ Hosp, Dept Pathol, SE-90185 Umea, Sweden,Department of Pathology, Umeå University Hospital, Umeå, Sweden,Norrland University Hospital
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- Behndig, Annelie F., 1963- (författare)
- Umeå University,Umeå universitet,Avdelningen för medicin,Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University, Umeå, Sweden,Umea Univ, Div Med, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden
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- Johansson, Mikael (författare)
- Umeå University,Umeå universitet,Onkologi,Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden,Umea Univ, Dept Radiat Sci, Oncol, SE-90185 Umea, Sweden
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- Planck, Maria (författare)
- Lund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Research Group Lung Cancer,Lund University Research Groups,Skåne University Hospital
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- Staaf, Johan (författare)
- Lund University,Lunds universitet,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Research Group Lung Cancer,Lund University Research Groups
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(creator_code:org_t)
- 2019-03-26
- 2019
- Engelska.
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
- Relaterad länk:
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https://doi.org/10.1...
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https://doi.org/10.1...
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Accurate histological classification and identification of fusion genes represent two cornerstones of clinical diagnostics in non-small cell lung cancer (NSCLC). Here, we present a NanoString gene expression platform and a novel platform-independent, single sample predictor (SSP) of NSCLC histology for combined, simultaneous, histological classification and fusion gene detection in minimal formalin fixed paraffin embedded (FFPE) tissue. The SSP was developed in 68 NSCLC tumors of adenocarcinoma (AC), squamous cell carcinoma (SqCC) and large-cell neuroendocrine carcinoma (LCNEC) histology, based on NanoString expression of 11 (CHGA, SYP, CD56, SFTPG, NAPSA, TTF-1, TP73L, KRT6A, KRT5, KRT40, KRT16) relevant genes for IHC-based NSCLC histology classification. The SSP was combined with a gene fusion detection module (analyzing ALK, RET, ROS1, MET, NRG1, and NTRK1) into a multicomponent NanoString assay. The histological SSP was validated in six cohorts varying in size (n = 11-199), tissue origin (early or advanced disease), histological composition (including undifferentiated cancer), and gene expression platform. Fusion gene detection revealed five EML4-ALK fusions, four KIF5B-RET fusions, two CD74-NRG1 fusion and three MET exon 14 skipping events among 131 tested cases. The histological SSP was successfully trained and tested in the development cohort (mean AUC = 0.96 in iterated test sets). The SSP proved successful in predicting histology of NSCLC tumors of well-defined subgroups and difficult undifferentiated morphology irrespective of gene expression data platform. Discrepancies between gene expression prediction and histologic diagnosis included cases with mixed histologies, true large cell carcinomas, or poorly differentiated adenocarcinomas with mucin expression. In summary, we present a proof-of-concept multicomponent assay for parallel histological classification and multiplexed fusion gene detection in archival tissue, including a novel platform-independent histological SSP classifier. The assay and SSP could serve as a promising complement in the routine evaluation of diagnostic lung cancer biopsies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Pathology
- Patologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Karlsson, Anna
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Cirenajwis, Hele ...
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Ericson-Lindquis ...
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Brunnström, Hans
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Reuterswärd, Chr ...
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Jönsson, Mats
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visa fler...
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Ortiz-Villalon, ...
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Hussein, Aziz
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Bergman, Bengt
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Vikström, Anders ...
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Monsef, Nastaran ...
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Brandén, Eva
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Koyi, Hirsh
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de Petris, Luigi
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Micke, Patrick
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Patthey, Annika
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Behndig, Annelie ...
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Johansson, Mikae ...
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Planck, Maria
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Staaf, Johan
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Scientific Repor ...
- Av lärosätet
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Uppsala universitet
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Umeå universitet
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Linköpings universitet
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Karolinska Institutet
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Lunds universitet