scholarly journals Next-Generation Sequencing Analysis of Endometrial Screening Liquid-Based Cytology Specimens: A Comparative Study to Tissue Specimens

2020 ◽  
Author(s):  
Toshiaki Akahane ◽  
Ikumi Kitazono ◽  
Shintaro Yanazume ◽  
Masaki Kamio ◽  
Shinichi Togami ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Next Generation Sequencing ◽  
Gene Panel ◽  
Molecular Testing ◽  
Sequencing Analysis ◽  
Cancer Gene ◽  
Next Generation ◽  
Ffpe Tissues ◽  
Liquid Based Cytology ◽  
Generation Sequencing

Abstract Background: Liquid-based cytology (LBC) is now a widely used method for cytologic screening and cancer diagnosis. Since the cells are fixed with alcohol-based fixatives, and the specimens are stored in a liquid condition, LBC specimens are suitable for genetic analyses. Methods: Here, we established a small cancer gene panel, including 60 genes and 17 microsatellite markers for next-generation sequencing, and applied to residual LBC specimens obtained by endometrial cancer screening to compare with corresponding formalin-fixed paraffin-embedded (FFPE) tissues. Results: A total of 49 FFPE and LBC specimens (n=24) were analyzed, revealing characteristic mutations for endometrial cancer, including PTEN, CTNNB1, PIK3CA, and PIK3R1 mutations. Eight cases had higher scores for both tumor mutation burden (TMB) and microsatellite instability (MSI), which agree with defective mismatch repair (MMR) protein expression. Paired endometrial LBC, and biopsied and/or resected FFPE tissues from 7 cases, presented almost identical mutations, TMB, and MSI profiles in all cases. Conclusion: These findings demonstrate that our ad hoc cancer gene panel enabled the detection of therapeutically actionable gene mutations in endometrial LBC and FFPE specimens. Endometrial cancer LBC specimens offer an alternative and affordable source of molecular testing materials.

scholarly journals Next-Generation Sequencing Analysis of Endometrial Screening Liquid-Based Cytology Specimens A Comparative Study to Tissue Specimens

2020 ◽  
Author(s):  
Toshiaki Akahane ◽  
Ikumi Kitazono ◽  
Shintaro Yanazume ◽  
Masaki Kamio ◽  
Shinichi Togami ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Next Generation Sequencing ◽  
Gene Panel ◽  
Molecular Testing ◽  
Sequencing Analysis ◽  
Cancer Gene ◽  
Next Generation ◽  
Ffpe Tissues ◽  
Liquid Based Cytology ◽  
Generation Sequencing

Abstract Background: Liquid-based cytology (LBC) is now a widely used method for cytologic screening and cancer diagnosis. Since the cells are fixed with alcohol-based fixatives, and the specimens are stored in a liquid condition, LBC specimens are suitable for genetic analyses. Methods: Here, we established a small cancer gene panel, including 60 genes and 17 microsatellite markers for next-generation sequencing, and applied to residual LBC specimens obtained by endometrial cancer screening to compare with corresponding formalin-fixed paraffin-embedded (FFPE) tissues. Results: A total of 49 FFPE and LBC specimens (n=24) were analyzed, revealing characteristic mutations for endometrial cancer, including PTEN, CTNNB1, PIK3CA, and PIK3R1 mutations. Eight cases had higher scores for both tumor mutation burden (TMB) and microsatellite instability (MSI), which agree with defective mismatch repair (MMR) protein expression. Paired endometrial LBC, and biopsied and/or resected FFPE tissues from 7 cases, presented almost identical mutations, TMB, and MSI profiles in all cases. Conclusion: These findings demonstrate that our ad hoc cancer gene panel enabled the detection of therapeutically actionable gene mutations in endometrial LBC and FFPE specimens. Endometrial cancer LBC specimens offer an alternative and affordable source of molecular testing materials.

scholarly journals Next-Generation Sequencing Analysis of Endometrial Screening Liquid-Based Cytology Specimens A Comparative Study to Tissue Specimens

2020 ◽  
Author(s):  
Toshiaki Akahane ◽  
Ikumi Kitazono ◽  
Shintaro Yanazume ◽  
Masaki Kamio ◽  
Shinichi Togami ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Next Generation Sequencing ◽  
Gene Panel ◽  
Molecular Testing ◽  
Sequencing Analysis ◽  
Cancer Gene ◽  
Next Generation ◽  
Ffpe Tissues ◽  
Liquid Based Cytology ◽  
Generation Sequencing

Abstract Background: Liquid-based cytology (LBC) is now a widely used method for cytologic screening and cancer diagnosis. Since the cells are fixed with alcohol-based fixatives, and the specimens are stored in a liquid condition, LBC specimens are suitable for genetic analyses. Methods: Here, we established a small cancer gene panel, including 60 genes and 17 microsatellite markers for next-generation sequencing, and applied to residual LBC specimens obtained by endometrial cancer screening to compare with corresponding formalin-fixed paraffin-embedded (FFPE) tissues. Results: A total of 49 FFPE and LBC specimens (n=24) were analyzed, revealing characteristic mutations for endometrial cancer, including PTEN, CTNNB1, PIK3CA, and PIK3R1 mutations. Eight cases had higher scores for both tumor mutation burden (TMB) and microsatellite instability (MSI), which agree with defective mismatch repair (MMR) protein expression. Paired endometrial LBC, and biopsied and/or resected FFPE tissues from 7 cases, presented almost identical mutations, TMB, and MSI profiles in all cases. Conclusion: These findings demonstrate that our ad hoc cancer gene panel enabled the detection of therapeutically actionable gene mutations in endometrial LBC and FFPE specimens. Endometrial cancer LBC specimens offer an alternative and affordable source of molecular testing materials.

scholarly journals Analysis by Next-Generation Sequencing Panel Covered 60 Genes and 17 Microsatellite Foci in Endometrial Screening Liquid-Based Cytology Specimens A Comparative Study to Tissue Specimens

2020 ◽  
Author(s):  
Toshiaki Akahane ◽  
Ikumi Kitazono ◽  
Shintaro Yanazume ◽  
Masaki Kamio ◽  
Shinichi Togami ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Next Generation Sequencing ◽  
Cancer Screening ◽  
Gene Panel ◽  
Cancer Gene ◽  
Next Generation ◽  
Small Cancer ◽  
Ffpe Tissues ◽  
Liquid Based Cytology ◽  
Generation Sequencing

Abstract Background Liquid-based cytology (LBC) is now a widely used method for cytologic screening and diagnosis of cancers. Since the cells are fixed with alcohol-based fixatives and the specimens are stored in a liquid condition, LBC specimens are also conducive for genetic analysis. Methods Here, we established a small cancer gene panel including 60 genes and 17 microsatellite markers for next-generation sequencing and applied to residual LBC specimens obtained by endometrial cancer screening to compare with corresponding formalin-fixed paraffin-embedded (FFPE) tissues. Results A total of 53 FFPE and LBC specimens (n=24) were analyzed, revealing characteristic mutations for endometrial cancer including those of PTEN, CTNNB1, PIK3CA, and PIK3R1 . Eight cases had higher scores for both tumor mutation burden (TMB) and microsatellite instability (MSI), which agree with defective mismatch repair (MMR) protein expression. Paired endometrial LBC, and biopsied and/or resected FFPE tissues from 7 cases, demonstrated almost the same mutations, TMB, and MSI profiles in all cases. Conclusion These findings demonstrate that the small cancer gene panel proved to be able to detect therapeutically actionable gene mutations in endometrial LBC and FFPE specimens and that LBC specimens obtained by endometrial cancer screening is an alternative and useful source of molecular testing.

scholarly journals Synchronous Pulmonary Adenocarcinomas

2020 ◽  
Vol 154 (1) ◽  
pp. 57-69
Author(s):  
Carlos A Pagan ◽  
Catherine A Shu ◽  
John P Crapanzano ◽  
Galina G Lagos ◽  
Mark B Stoopler ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Gene Panel ◽  
Driver Mutations ◽  
Molecular Testing ◽  
Next Generation ◽  
Synchronous Tumors ◽  
Targeted Next Generation Sequencing ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Abstract Objectives To determine concordance/discordance between morphology and molecular testing (MT) among synchronous pulmonary carcinomas using targeted next generation sequencing (NGS), with and without comprehensive molecular review (CMR), vs analyses of multiple singe genes (non-NGS). Methods Results of morphologic and MT assessment were classified as concordant, discordant, or indeterminate. For discordant cases, comprehensive histologic assessment (CHA) was performed. Results Forty-seven cases with 108 synchronous tumors were identified and underwent MT (NGS, n = 23 and non-NGS, n = 24). Histology and MT were concordant, discordant, and indeterminate in 53% (25/47), 21% (10/47), and 26% (12/47) of cases, respectively. CHA of the 10 discordant cases revised results of three cases. Conclusions There is discordance between histology and MT in a subset of cases and MT provides an objective surrogate for staging synchronous tumors. A limited gene panel is sufficient for objectively assessing a relationship if the driver mutations are distinct. Relatedness of mutations require CMR with a larger NGS panel (eg, 50 genes).

scholarly journals Improved Molecular Diagnosis of Aplastic Anemia/Bone Marrow Failure Syndromes Using a Novel Comprehensive Next Generation Sequencing Gene Panel

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4790-4790
Author(s):  
Majed Dasouki ◽  
Syed Osman Ahmed ◽  
Ali Alahmari ◽  
Amal Jabr ◽  
Moheeb Ali Alawwami ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Next Generation Sequencing ◽  
Aplastic Anemia ◽  
Molecular Diagnosis ◽  
Bone Marrow Failure ◽  
Gene Panel ◽  
Sequencing Analysis ◽  
Next Generation ◽  
Bone Marrow Failure Syndromes ◽  
Generation Sequencing

Abstract Introduction: Various forms of aplastic anemia (AA)/bone marrow failure syndromes (IBMFs) show significant clinical and molecular heterogeneity with significant clinical overlap and are often diagnosed based on established clinical and pathological criteria. While >70 genes have been identified in patients with AA/IBMFs, most cases have are labelled as idiopathic with no identifiable genetic abnormlaity found. Precise detection of genetic abnormalities in these patients may assist in more accurate molecular diagnosis in these patients, proper counseling, cancer surveillance and personalized clinical intervention. Method: As part of the Saudi Human Genome Project, we developed a comprehensive 405 gene panel encompassing all known Mendelian hematological disorders (hemolytic anemias, aplastic anemias/bone marrow failure syndromes, coagulation disorders) using the Ion Torrent AmpliSeq technology. Patients who met the clinical diagnosis of aplastic anemia/bone marrow failure syndrome were enrolled into this study. Peripheral blood samples were subjected to this next-generation sequencing analysis. Results: We validated the Saudi Mendeliome assay using 642 samples with known mutations across various medical specialties. We then tested 37 patients with AA/IBMFS using this Proton-Ion sequencing platform. Mutations were identified in 7/37 (19%) of patients, followed by whole exome sequencing (WES) in those patients without identifiable mutations. Conclusion: Compared with clinical WES and/or whole genome sequencing (WGS), which are still expensive, time consuming and difficult to interpret, this novel and comprehensive targeted gene panel is more economical (< $150), faster (3-4 weeks), upgradable (by spiking in newly identified AA/IBMFs genes) and can be used to genotype patients with acquired aplastic anemia/bone marrow failure syndromes and guide their management. Second tier testing using WES/WGS is recommended for cases without identifiable mutations. Disclosures No relevant conflicts of interest to declare.

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