scholarly journals FrenchFISH: Poisson Models for Quantifying DNA Copy Number From Fluorescence In Situ Hybridization of Tissue Sections

2021 ◽  
pp. 176-186
Author(s):  
Geoff Macintyre ◽  
Anna M. Piskorz ◽  
Adam Berman ◽  
Edith Ross ◽  
David B. Morse ◽  
...  

PURPOSE Chromosomal aberration and DNA copy number change are robust hallmarks of cancer. The gold standard for detecting copy number changes in tumor cells is fluorescence in situ hybridization (FISH) using locus-specific probes that are imaged as fluorescent spots. However, spot counting often does not perform well on solid tumor tissue sections due to partially represented or overlapping nuclei. MATERIALS AND METHODS To overcome these challenges, we have developed a computational approach called FrenchFISH, which comprises a nuclear volume correction method coupled with two types of Poisson models: either a Poisson model for improved manual spot counting without the need for control probes or a homogeneous Poisson point process model for automated spot counting. RESULTS We benchmarked the performance of FrenchFISH against previous approaches using a controlled simulation scenario and tested it experimentally in 12 ovarian carcinoma FFPE-tissue sections for copy number alterations at three loci (c-Myc, hTERC, and SE7). FrenchFISH outperformed standard spot counting with 74% of the automated counts having < 1 copy number difference from the manual counts and 17% having < 2 copy number differences, while taking less than one third of the time of manual counting. CONCLUSION FrenchFISH is a general approach that can be used to enhance clinical diagnosis on sections of any tissue by both speeding up and improving the accuracy of spot count estimates.

2018 ◽  
Author(s):  
Geoff Macintyre ◽  
Anna M Piskorz ◽  
Edith Ross ◽  
David B Morse ◽  
Ke Yuan ◽  
...  

Chromosomal aberration and DNA copy number change are robust hallmarks of cancer. Imaging of spots generated using fluorescence in situ hybridisation (FISH) of locus specific probes is routinely used to detect copy number changes in tumour nuclei. However, it often does not perform well on solid tumour tissue sections, where partially represented or overlapping nuclei are common. To overcome these challenges, we have developed a computational approach called FrenchFISH, which comprises a nuclear volume correction method coupled with two types of Poisson models: either a Poisson model for improved manual spot counting without the need for control probes; or a homogenous Poisson Point Process model for automated spot counting. We benchmarked the performance of FrenchFISH against previous approaches in a controlled simulation scenario and exemplify its use in 12 ovarian cancer FFPE-tissue sections, for which we assess copy number alterations in three loci (c-Myc, hTERC and SE7). We show that FrenchFISH outperforms standard spot counting approaches and that the automated spot counting is significantly faster than manual without loss of performance. FrenchFISH is a general approach that can be used to enhance clinical diagnosis on sections of any tissue.


2008 ◽  
Vol 182 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Zsuzsa Rákosy ◽  
Laura Vízkeleti ◽  
Szilvia Ecsedi ◽  
Ágnes Bégány ◽  
Gabriella Emri ◽  
...  

2018 ◽  
Vol 142 (10) ◽  
pp. 1254-1259 ◽  
Author(s):  
Katherine B. Geiersbach ◽  
Julia A. Bridge ◽  
Michelle Dolan ◽  
Lawrence J. Jennings ◽  
Diane L. Persons ◽  
...  

Context.— Fluorescence in situ hybridization (FISH) and brightfield in situ hybridization (ISH) are 2 clinically approved laboratory methods for detecting ERBB2 (HER2) amplification in breast cancer. Objective.— To compare the performance of FISH and brightfield ISH on proficiency testing administered by the College of American Pathologists Laboratory Accreditation Program. Design.— Retrospective review was performed on 70 tissue core samples in 7 separate proficiency testing surveys conducted between 2009 and 2013. Results.— The samples included 13 consensus-amplified tissue cores, 53 consensus-nonamplified cores, and 4 cores that did not reach consensus for FISH and/or brightfield ISH. There were 2552 individual responses for FISH and 1871 individual responses for brightfield ISH. Consensus response rates were comparable for FISH (2474 of 2524; 98.0%) and brightfield ISH (2135 of 2189; 97.5%). The FISH analysis yielded an average HER2 copy number per cell that was significantly higher (by 2.86; P = .02) compared with brightfield ISH for amplified cores. For nonamplified cores, FISH yielded slightly, but not significantly, higher (by 0.17; P = .10) HER2 copy numbers per cell. There was no significant difference in the average HER2 to control ratio for either consensus-amplified or consensus-nonamplified cores. Participants reported “unable to analyze” more frequently for brightfield ISH (244 of 2453; 9.9%) than they did for FISH (160 of 2684; 6.0%). Conclusions.— Our study indicates a high concordance rate in proficiency testing surveys, with some significant differences noted in the technical performance of these assays. In borderline cases, updated American Society of Clinical Oncology/College of American Pathologists cutoff thresholds that place greater emphasis on HER2 copy number per cell could accentuate those differences between FISH and brightfield ISH.


2015 ◽  
Vol 305 (7) ◽  
pp. 709-718 ◽  
Author(s):  
Annett Petrich ◽  
Pablo Rojas ◽  
Julia Schulze ◽  
Christoph Loddenkemper ◽  
Lorenzo Giacani ◽  
...  

2004 ◽  
Vol 150 (1) ◽  
pp. 22-26 ◽  
Author(s):  
Yosuke Matsumoto ◽  
Kenichi Nomura ◽  
Sawako Matsumoto ◽  
Kyoji Ueda ◽  
Mitsushige Nakao ◽  
...  

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