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法国 FISH：基于组织切片荧光原位杂交定量 DNA 拷贝数的鱼类模型。

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

机构信息

Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, UK.

Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK.

出版信息

JCO Clin Cancer Inform. 2021 Feb;5:176-186. doi: 10.1200/CCI.20.00075.

DOI:10.1200/CCI.20.00075
PMID:33570999
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8140799/
Abstract

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.

摘要

目的

染色体畸变和 DNA 拷贝数变化是癌症的显著特征。使用针对特定基因座的探针进行荧光原位杂交（FISH）是检测肿瘤细胞拷贝数变化的金标准，这些探针以荧光点的形式成像。然而，由于部分代表性或重叠的细胞核，点计数在实体肿瘤组织切片上的效果往往不佳。

材料和方法

为了克服这些挑战，我们开发了一种称为 FrenchFISH 的计算方法，该方法包括核体积校正方法和两种泊松模型：一种是改进手动点计数的泊松模型，无需使用对照探针；另一种是用于自动点计数的同质泊松点过程模型。

结果

我们使用受控模拟场景对 FrenchFISH 的性能进行了基准测试，并在 12 个卵巢癌 FFPE 组织切片中针对三个基因座（c-Myc、hTERC 和 SE7）的拷贝数改变进行了实验测试。FrenchFISH 的性能优于标准的点计数，74%的自动计数与手动计数的拷贝数差异小于 1，17%的自动计数与手动计数的拷贝数差异小于 2，而用时不到手动计数的三分之一。

结论

FrenchFISH 是一种通用方法，可通过加快和提高点计数估计的准确性来增强任何组织切片的临床诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/1959667685d6/cci-5-cci.20.00075-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/53e5124a6c9e/cci-5-cci.20.00075-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/47eaed94ae36/cci-5-cci.20.00075-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/05dc54253ba6/cci-5-cci.20.00075-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/cab3b5c8ef3f/cci-5-cci.20.00075-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/bb3b46913613/cci-5-cci.20.00075-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/1959667685d6/cci-5-cci.20.00075-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/53e5124a6c9e/cci-5-cci.20.00075-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/47eaed94ae36/cci-5-cci.20.00075-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/05dc54253ba6/cci-5-cci.20.00075-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/cab3b5c8ef3f/cci-5-cci.20.00075-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/bb3b46913613/cci-5-cci.20.00075-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ec9/8140799/1959667685d6/cci-5-cci.20.00075-g006.jpg

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