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Detecting breast cancer

A technology for cancer and biological samples, applied in the field of breast cancer detection, which can solve problems such as inability to accurately identify women

Pending Publication Date: 2020-09-11
MAYO FOUND FOR MEDICAL EDUCATION & RES +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Effective preventive therapies exist, but current risk prediction models do not accurately identify the majority of women at increased risk of breast cancer (see eg Pankratz VS et al, J Clin Oncol 2008 Nov 20;26(33):5374- 9)

Method used

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  • Detecting breast cancer
  • Detecting breast cancer
  • Detecting breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0444] This example describes the discovery and tissue validation of breast cancer specific markers.

[0445] Table 1 shows the number of tissue samples for each breast cancer subtype used in the discovery of breast cancer specific markers.

[0446] Table 1.

[0447]

[0448] For the discovery of methylation markers by RRBS, frozen tissue samples were obtained from 72 invasive breast cancer cases (18 luminal A, 18 luminal B, 18 basal-like / triple negative and 18 HER2+), 15 Aggressive breast cancer from patients with germline BRCA mutations (6 BRCA1, 9 BRCA2) and 45 controls (18 normal breasts (reducing mammoplasty or preventive mastectomy), germline BRCA carriers in Nine histologically normal breasts (prophylactic mastectomy) and 18 normal buffy coats were obtained. Tumor and breast tissue sections were reviewed by an experienced gastrointestinal pathologist to confirm the diagnosis and estimate abnormal cellularity. The sections were then subjected to macroscopic dissect...

Embodiment II

[0528] This example describes tissue validation of breast cancer specific markers.

[0529] Individual tissue samples (fresh frozen) were selected from the Institutional Cancer Registry at the Mayo Clinic Rochester and reviewed by experienced pathologists to confirm correct classification and to guide macroscopic dissection. Cases included 29 triple-negative / basal-like invasive breast cancers, 34 HER2 invasive breast cancers, 36 luminal A invasive breast cancers, and 25 luminal B invasive breast cancers. Also included were 5 BRCA1 cancers and 6 BRCA2 cancers, 21 HGD DCIS and 12 LGD DCIS. Controls included 27 age-matched normal breast tissue and 18 buffy coat samples from normal women.

[0530] The 55 methylated DNA markers (MDMs) were selected from a list of 80 MDMs tested with discovery samples (see Example 1 and Tables 11-15).

[0531] Genomic DNA was prepared using the QIAamp DNA Mini Kit (Qiagen, Valencia CA) and bisulfite transformed using the EZ-96 DNA Methylation Kit ...

Embodiment III

[0557] This example describes the identification of breast tissue and plasma markers for the detection of breast cancer.

[0558] Candidate methylation markers for detection of breast cancer were identified by RRBS on breast cancer and normal breast tissue samples. 58 markers were initially identified, and target-enriched long probe quantitative amplification signal assays were designed and ordered (for general techniques, see e.g. WO2017 / 075061 and US Patent Application Serial No. 15,841,006) (Table 18 shows the Methylated regions with normal breast tissue) (Table 19 and Table 20 show the primer and probe sequences for the markers shown in Table 18). After design screening and redesign, 56 markers (see Table 21) were selected and assayed, triplicated and tested with tissues. Assays were split equally between FAM and HEX reports and triplexed with reference assay B3GALT6 reporting on Quasar670.

[0559] Table 18. Methylated regions that distinguish breast cancer tissue from ...

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PUM

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Abstract

Provided herein is technology for breast cancer screening and particularly, but not exclusively, to methods, compositions, and related uses for detecting the presence of breast cancer.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims priority to and the benefit of US Provisional Application No. 62 / 592,828, filed November 30, 2017, the contents of which are hereby incorporated by reference in their entirety. [0003] Field of Invention [0004] Provided herein are techniques for breast cancer screening, and in particular, but not exclusively, to methods, compositions, and related uses for detecting the presence of breast cancer. Background technique [0005] Breast cancer affects approximately 230,000 American women and takes approximately 40,000 lives each year. Although carriers of germline mutations in the BRCA1 and BRCA2 genes are known to be at high risk for breast cancer, most women with breast cancer do not have a mutation in one of these genes and are accurately identified in The ability of women at increased breast cancer risk is limited. Effective preventive therapies exist, but current risk prediction models do not...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886
CPCC12Q1/6886C12Q2600/154C12Q2600/16G16H50/20C12Q1/6853G16H50/30C12Q1/6806C12Q1/6809C12Q1/6811C12Q2537/143C12Q1/6837C12Q2600/158C12Q2600/118C12Q2600/112C12Q2600/106C12Q1/6827C12Q1/682C12Q2600/156
Inventor 大卫·A·阿尔奎斯特威廉·R·泰勒道格拉斯·W·马奥尼特蕾西·C·亚卜约翰·B·基谢尔哈特姆·T·阿拉维格雷厄姆·P·利德加德迈克尔·W·凯泽
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
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