Colon cancer methylation markers and uses thereof
Inventors
Zhang, Kang • Hou, Rui • Zheng, Lianghong
Assignees
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Publication Number
US-12351876-B2
Publication Date
2025-07-08
Expiration Date
2037-07-06
Abstract
Disclosed herein are methods and kits for identifying a subject as having colon cancer. Also provided herein are methods and kits for determining the prognosis of a subject having colon cancer and for determining the progression of colon cancer in a subject.
Core Innovation
The invention provides methods and kits for identifying a subject as having colon cancer by generating a methylation profile based on specific biomarkers from genomic DNA obtained from a biological sample of the subject. The methods involve processing the genomic DNA with a deaminating agent, generating the methylation profile of one or more biomarkers, comparing this profile to a control, and identifying the subject as having colon cancer if the profile correlates to the control. Then, an effective amount of a therapeutic agent can be administered to the subject identified as having colon cancer.
Furthermore, the invention includes methods and kits for determining the prognosis of a subject having colon cancer and for monitoring the progression of colon cancer in a subject. This involves generating a methylation profile comprising selected biomarkers, obtaining a methylation score based on the profile, and guiding treatment decisions such as initiating treatment, adjusting dosage, switching agents, or treating relapse based on the methylation score.
The problem being solved is that existing diagnostic procedures for colon cancer often start only after symptoms appear, which leads to costly, invasive, and sometimes time-consuming procedures. Additionally, inaccessible areas can prevent accurate diagnosis, and late diagnosis is associated with high mortality and morbidity. This invention addresses the need for sensitive, accurate, and less invasive methods for diagnosing colon cancer, determining prognosis, and monitoring treatment progression.
Claims Coverage
The claims cover four main inventive features related to diagnosing and treating colon cancer using methylation profiles from genomic DNA.
Methylation profiling of biomarkers for colon cancer diagnosis and treatment selection
Methods of obtaining treated genomic DNA from a cell-free DNA sample, performing next-generation sequencing to determine methylation status of specific biomarkers including cg10673833 and cg08088171, generating a methylation profile, identifying colon cancer by comparison with controls, and administering therapeutic agents accordingly.
Expanded methylation profiling including additional biomarkers
Including methylation data of cg13420112, cg14642259, cg20973720, cg27536151, cg24741563, and cg22979615 in the methylation profile for colon cancer diagnosis and treatment.
Use of biological samples such as blood for obtaining cfDNA
The use of a cell-free DNA sample obtained from blood as the source of genomic DNA for methylation analysis.
Treatment of extracted genomic DNA for methylation analysis
Extracting genomic DNA from cfDNA samples and treating with a deaminating agent to prepare the DNA for methylation analysis suitable for detecting methylation status of the biomarkers.
Application of digital PCR sequencing methods in methylation analysis
Utilizing digital PCR sequencing techniques as the next-generation sequencing method for methylation analysis.
Use in metastatic and relapsed or refractory colon cancer
The methods and methylation profiling are applicable to identifying and treating metastatic, relapsed, or refractory forms of colon cancer.
The claims collectively describe methods for methylation-based diagnosis of colon cancer using specific biomarkers, processing of genomic DNA for methylation analysis, use of next-generation sequencing including digital PCR, application to various colon cancer forms including metastatic and relapsed, and consequent administration of defined therapeutic agents based on methylation profile results.
Stated Advantages
Provides sensitive and specific diagnosis of colon cancer based on DNA methylation profiling.
Allows early detection of colon cancer potentially before symptoms develop, thereby reducing costly and invasive procedures associated with late diagnosis.
Enables determination of prognosis and monitoring of cancer progression through methylation score, aiding in personalized treatment planning.
Utilizes minimally invasive biological samples such as blood, tissue biopsy, or circulating tumor cells to obtain genomic DNA.
Supports use of machine learning methods to improve accuracy and differentiation between colon cancer and other cancer types.
Documented Applications
Identifying subjects as having colon cancer using methylation profiles of specific biomarkers.
Determining the prognosis of a subject having colon cancer and monitoring the progression of colon cancer by analyzing methylation scores.
Selecting treatment options and managing dosage based on methylation profiling and prognosis assessment.
Use of kits comprising nucleic acid probes hybridizing to predictive methylation biomarkers for colon cancer diagnosis and prognosis.
Application of the methods to various forms of colon cancer including metastatic, relapsed, refractory, adenocarcinoma, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, primary colorectal lymphoma, leiomyosarcoma, melanoma, and squamous cell carcinoma.
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