Abstract 4984
Background
Mismatch repair deficiency (dMMR) due to germline mutations in DNA repair genes including MLH1, MSH2, MSH6 and PMS2, or somatic aberrant silencing of MLH1, is a well-established feature for Lynch syndrome, a major type of hereditary colorectal cancer (CRC). The purpose of this study is to derive prevalence of germline MMR gene mutations in Chinese population with dMMR CRC.
Methods
ColonCore panel is designed for simultaneous detection of microsatellite instabiligy (MSI) status of 22 regions and mutations in 38 CRC-related genes. Whole exons of the 38 genes were covered by the panel. The MSI phenotype detection method was a read-count-distribution-based approach. It utilized the coverage ratio of a specific set of repeat lengths as the main characteristic of each microsatellite locus, and categorized a locus as unstable if the coverage ratio was less than a given threshold. The MSI status of a sample was determined by the percentage of unstable loci in the given sample.
Results
Among 1394 postsurgical CRC patients whose MMR status were detected by immunohistochemistry (IHC), 99 patients were dMMR, accounting for 7.1%. The concordance rate was 92.3% between MSI and IHC. Next, we investigated the germline mutation spectrum of dMMR patients. About 26.3% patients harbored pathogenic germline MMR gene mutations, with 13%, 6%, 5% and 2% of patients carrying pathogenic MLH1, MSH2, MSH6 and PMS2 mutations, respectively. Specially, about 30% pathogenic MLH1 mutation occured in splice region. Among patients with pathogenic MMR gene mutations, their first cancer was diagnosed ranging from 22 to 69 years old with median age at diagnosis was 50, and only 57% have a family history of ≥ 1 relative with Lynch syndrome related cancers. Furthermore, 3% harbored pathogenic mutations in other genes. Approximately, 17% of patients harbored MMR gene variants of unknown significance (VUS) and 26% harbored other VUS. The remaining 28% of patients had no pathogenic or VUS mutations from this panel.
Conclusions
The prevalence rate of germline pathogenic mutations is 26% in dMMR CRC patients, accounting for 1.8% of all resectable CRC patients. Median age at diagnosis of Lynch syndrome related cancers is 50 years old and nearly 40% Lynch syndrome patients have no family history.
Clinical trial identification
Legal entity responsible for the study
Ying Yuan.
Funding
Burning Rock Biotech.
Editorial Acknowledgement
Disclosure
C. Liu: Burning Rock Biotech. All other authors have declared no conflicts of interest.
Resources from the same session
1159 - Molecular characterization and search for founding effects in Canarian families with Hereditary Breast and Ovarian Cancer Syndrome
Presenter: Elisenda Llabres Valenti
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3725 - Effect of the polymorphism rs2066844 of the NOD2 gene on colon cancer incidence in a high cardiovascular risk population. Modulation by gender
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3708 - Effect of the polymorphisms rs1476413, rs1801131, rs4846052 and rs6541003 of the MTHFR gene on prostate cancer in a high cardiovascular risk population
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5057 - Association of a genetic variant in cyclin-dependent kinase Inhibitor 2A gene with the increased risk of breast cancer
Presenter: Soodabeh Shahid Sales
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5970 - Investigating the role of HAT protein TIP60 in regulating functional dynamics of nuclear receptor PXR
Presenter: KARISHMA BAKSHI
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1360 - The role of downregulated SIRT3 expression in patients with hepatocellular carcinoma
Presenter: Hanhee Jo
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1634 - Prediction and Intervention of Colorectal Cancer Risk with Artificial Intelligent System
Presenter: Yang Ge
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4921 - Measuring the Efficiency of Cancer Care in Europe
Presenter: Rikard Althin
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1235 - Circulating cell-free DNA isolated from plasma of mesenteric veins predicts prognosis in stage II colorectal cancer patients
Presenter: Chih-Yung Yang
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5169 - _lonality of uterine carcinosarcoma as a factor of clinical prognosis.
Presenter: Natalia Levitskaya
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract