GI Polyps and Polyposis in Individuals Harboring Germline CHEK2 Mutations
Corey Chang1,2, John E Lee1, Kevin M Waters1
1Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Diseases of the Colon and Rectum
|July 3, 2024
Summary
Germline checkpoint kinase 2 (CHEK2) mutations are linked to gastrointestinal polyposis. Patients with CHEK2 mutations, particularly the p.S428F variant, show a high incidence of right-sided colon adenomas, warranting targeted colonoscopies.
Area of Science:
- Oncology
- Genetics
- Gastroenterology
Background:
- Checkpoint kinase 2 (CHEK2) is a crucial tumor suppressor gene within the DNA damage response pathway.
- Germline mutations in CHEK2 are implicated in various cancers, and its association with gastrointestinal polyposis is increasingly recognized.
- Genetic testing for CHEK2 mutations is recommended for individuals with a history of multiple colon polyps.
Purpose of the Study:
- To investigate the association between germline CHEK2 mutations and attenuated or oligopolyposis.
- To characterize the gastrointestinal clinicopathologic profile of patients with germline CHEK2 mutations.
- To identify specific CHEK2 mutation patterns associated with polyp development and characteristics.
Main Methods:
- A retrospective observational study design was employed.
- Medical records of 45 patients with confirmed germline CHEK2 mutations, who underwent endoscopic examinations between 1999 and 2020, were reviewed.
- Clinicopathologic variables, including polyp type, location, and number, were systematically described and analyzed.
Main Results:
- Twenty-five out of 45 patients (55.6%) exhibited gastrointestinal polyps, with 17 having lower GI polyps.
- Common CHEK2 mutations found in patients with polyps included p.S428F (n=10), p.I157T (n=4), and p.T476M (n=2).
- Five patients (11.1%) developed colorectal adenocarcinoma, and patients with the p.S428F mutation predominantly had right-sided adenomas (50%).
Conclusions:
- Germline CHEK2 mutations should be considered in the diagnostic workup of patients presenting with polyposis.
- The observed high frequency of right-sided adenomas in patients with p.S428F CHEK2 mutations underscores the importance of thorough right-sided colonoscopies.
- Further research may elucidate the specific mechanisms linking CHEK2 mutations to distinct polyp phenotypes and cancer risks.
Related Concept Videos
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
01:33Cancer-Critical Genes I: Proto-oncogenes
8.8K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.8K
01:35Pedigree Analysis
84.2K
Overview
84.2K
02:21Cancers Originate from Somatic Mutations in a Single Cell
11.9K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
11.9K
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
7.4K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
7.4K
01:20The Retinoblastoma Gene
4.1K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K