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Detecting endometrial cancer

A human and genetic technology, applied in the field of detection of endometrial cancer, can solve the problem of lack of early detection methods for EC

Pending Publication Date: 2021-10-26
MAYO FOUND FOR MEDICAL EDUCATION & RES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Although endometrial cancer (EC) is the most common gynecological malignancy in the United States and many other developed countries, methods for early detection of EC are lacking (see Siegel, R.L. et al., Cancer statistics, 2016. CA Cancer J Clin, 2016.66(1 ): 7-30 pages; Parkin, D. et al., Global cancer statistics, 2002.CA Cancer JClin., 2005.55(2): 74-108 pages)

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  • Detecting endometrial cancer
  • Detecting endometrial cancer
  • Detecting endometrial cancer

Examples

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Embodiment I

[0556] This example describes selective discovery and validation by permethylation analysis for the detection of endometrial carcinoma (EC) and EC histological subtypes (e.g., serous EC, clear cell EC, carcinosarcoma EC, and endometrioid EC). EC) novel DNA methylation markers.

[0557] Uses proprietary methods of sample preparation, sequencing, analysis pipelines, and filters to identify and narrow down differentially methylated regions (DMRs) to those that can pinpoint EC and various EC histological subtypes (e.g., serous EC, clear cell EC, carcinosarcoma EC, and endometrioid EC) and performed excellent DMR in clinical testing settings.

[0558] From tissue to tissue analysis, 318 hypermethylated EC DMRs were identified (Table 1). Table 2 presents the area under the curve and fold change compared to the EC control for the markers listed in Table 1.

[0559] Table 1. Identified methylated regions that distinguish endometrial cancer tissue from normal endometrial tissue.

[...

Embodiment II

[0645] This example describes the materials and methods of Example I.

[0646] sample:

[0647]Tissue and blood were obtained from the Mayo Clinic Biobank under institutional IRB oversight. The selection of samples strictly followed the subject research authorization and inclusion / exclusion criteria. Cancer subtypes include 1) serous EC, 2) clear cell EC, 3) carcinosarcoma EC, and 4) endometrioid EC. Controls included leukocytes derived from non-neoplastic tissue and whole blood. Tissues were macroscopically dissected and histology reviewed by a dedicated GI pathologist. Samples were age and sex matched, randomized and blinded. Purification from 113 frozen tissues (16 Grade 1 / 2 endometrioid (G1 / 2E), 16 grade 3 endometrioid (G3E), 11 serous, 11 clear cell EC, 15 uterine carcinosarcoma, 44 benign endometrium (BE) tissues (14 hyperplastic, 12 atrophic, 18 hyperplastic disorders), 70 formalin-fixed paraffin-embedded (FFPE) cervical carcinomas (CC) (36 squamous cell carcinoma...

Embodiment III

[0661] This example describes the identification of endometrial cancer tissue markers and plasma markers for the detection of breast cancer.

[0662] Candidate methylation markers for the detection of EC, clear cell EC, serous EC, carcinosarcoma EC, and endometrioid EC were identified by RRBS of EC tissue samples versus normal endometrial tissue samples. To identify methylated DNA markers, 165 samples per patient group (i.e., 19 benign, 34 adenocarcinoma, 36 squamous cell carcinoma, 15 carcinoma endometrial carcinoma, 11 clear cell intrauterine endometrial carcinoma, 5 endometrioid endometrial carcinoma grade 1, 11 endometrioid endometrial carcinoma grade 2, 16 endometrioid endometrial carcinoma grade 3 and 18 normal buffy coat) The RRBS process was performed and then compared to the bisulfite-converted human genome. CpG regions with high methylation ratios in endometrial cancer relative to normal endometrium and buffy coat were selected and mapped to their gene names.

[06...

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Abstract

Provided herein is technology for endometrial cancer (EC) screening and particularly, but not exclusively, to methods, compositions, and related uses for detecting the presence of endometrial cancer and various subtypes of endometrial cancer.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 796,384, filed January 24, 2019, which is incorporated herein by reference in its entirety. technical field [0003] Provided herein are techniques for screening for endometrial cancer (EC), and particularly, but not exclusively, methods, compositions and related uses for detecting the presence of endometrial cancer and various endometrial cancer subtypes. Background technique [0004] Although endometrial cancer (EC) is the most common gynecological malignancy in the United States and many other developed countries, methods for early detection of EC are lacking (see Siegel, R.L. et al., Cancer statistics, 2016. CA Cancer J Clin, 2016.66(1 ): pp. 7-30; Parkin, D. et al., Global cancer statistics, 2002. CA Cancer JClin., 2005.55(2): pp. 74-108). Although low-risk early EC has a good prognosis, with a 5-year overall survival (OS) rate of >...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6844
CPCC12Q2600/154C12Q1/6886G16B30/10G16B35/20C12Q2537/143
Inventor 威廉·R·泰勒约翰·B·基谢尔道格拉斯·W·马奥尼大卫·A·阿尔奎斯特哈特姆·T·阿拉维玛丽亚·贾库莫普洛斯
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
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