Lynch syndrome-associated colorectal cancer in a 16-year-old girl due to a de novo MSH2 mutation

2020 ◽  
Vol 13 (7) ◽  
pp. e233935
Author(s):  
Kristin Zajo ◽  
Susan I Colace ◽  
Danielle Mouhlas ◽  
Steven H Erdman
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
De Novo ◽  
Advanced Stage ◽  
Adult Onset ◽  
Cancer Syndrome ◽  
Poor Survival ◽  
Descending Colon ◽  
Unusual Finding ◽  
Hereditary Cancer Predisposition

The diagnosis of paediatric colorectal cancer is an unusual finding often diagnosed at an advanced stage with associated poor survival. Paediatric colorectal cancer warrants investigation for hereditary cancer predisposition syndromes, including Lynch syndrome. Here we describe a 16-year-old girl who presented with a stage IIA mucinous adenocarcinoma of the descending colon (T3 N0 M0) treated by resection alone that was associated with a pathogenic germline mutation of MSH2 (c.1786_1788delAAT (p.Asn596del)). This previously described mutation was not found in either parent or her three siblings. To our knowledge, this is the earliest reported case of paediatric Lynch syndrome-associated colorectal cancer by de novo mutation of MSH2. This case illustrates that although Lynch syndrome is typically described as an adult-onset cancer syndrome, Lynch syndrome-associated colorectal cancer can be found in children and adolescents. Genetic testing should be considered as a part of the initial evaluation in these patients.

scholarly journals Recent advances in understanding Lynch syndrome

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2889 ◽  
Author(s):  
Sherief Shawki ◽  
Matthew F. Kalady
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Correct Diagnosis ◽  
Diagnostic Testing ◽  
Gene Mutations ◽  
The United States ◽  
Cancer Syndrome ◽  
Dna Mismatch ◽  
Recent Developments ◽  
Risk Patients

Colorectal cancer affects about 4.4% of the population and is a leading cause of cancer-related death in the United States. Approximately 10% to 20% of cases occur within a familial pattern, and Lynch syndrome is the most common hereditary colorectal cancer syndrome. Lynch syndrome is a hereditary predisposition to forming colorectal and extracolonic cancers, caused by a germline mutation in one of the DNA mismatch repair genes. Identifying at-risk patients and making a correct diagnosis are the keys to successful screening and interventions which will decrease formation of and death from cancers. Knowledge of the genetics and the natural history of Lynch syndrome has continued to be uncovered in recent years, leading to a better grasp on how these patients and their families should be managed. Recent developments include the approach to diagnostic testing, more precise definitions of the syndrome and risk stratification based on gene mutations, surgical decision-making, and chemoprevention.

Chromosomal Aberration in Colorectal Cancer Family

2015 ◽  
Vol 15 (1) ◽  
pp. 8-11
Author(s):  
Edvins Miklasevics ◽  
Mikko Kupila ◽  
Dagnija Kalniete ◽  
Inese Eglite ◽  
Dace Berzina ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Chromosomal Aberration ◽  
Chromosomal Aberrations ◽  
Snp Array ◽  
Hereditary Cancer Syndrome ◽  
Coding Region ◽  
Cancer Syndrome ◽  
Increased Risk ◽  
Risk Of Malignancy

Summary Introduction. Lynch syndrome, previously more commonly known as hereditary nonpolyposis colorectal cancer, is a hereditary cancer syndrome with an autosomal dominant inheritance pattern. Usually it is caused by mutations the MMR genes. In 20 - 25% of cases patients are not found to have mutations in any of these genes. Chromosomal aberrations as a cause of the Lynch syndrome were examined in this study. Aim of the study. To identify chromosomal aberrations which may lead to colorectal cancer. Material and methods. Twelve patients, corresponding to either Amsterdam I/II criteria or Bethesda guidelines, which have been tested negative for mutations in Lynch genes have been karyotyped were karyotyped with SNP array chips, in order to determine if they had potentially heritable chromosomal aberrations which could be responsible for increased risk of malignancy. Results. One patient with a 14.7Mbp duplication framed by small deletions was chosen to be the most likely patient to suffer from an inherited carcinogenic chromosomal aberration. The preceding deletion was found to contain the coding region of BRE, encoding a component of the BRCA1-A complex; we believe that this deletion is the most carcinogenic component of the aberration and likely responsible for Lynch syndrome in this case. The larger duplication furthermore contained the coding regions for 83 genes, some of which have been shown to promote malignant disease when overexpressed. Conclusion. Because of the clinically grossly tolerable nature of the aberration it is possible that it was vertically transmitted and contributed to the onset of colorectal cancer in the patient and his mother and maternal aunt.

scholarly journals Clinical Prognosis of AKT2 and COX2 Mutation on Colorectal Cancer

2021 ◽  
Vol 6 (6) ◽  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Common Type ◽  
Cancer Syndrome ◽  
Degree Relative ◽  
Clinical Prognosis ◽  
Hereditary Predisposition ◽  
The Third ◽  
The World ◽  
Incidence Risk

Cancer has become one of the most mortal diseases in the world. It was estimated in 2018 18.1 millions new cancer cases. The colorectal cancer (CRC) is the third most common type of cancer in men and the second in women around the world [1]. The incidence risk in the occidental population is 5% to 6%, and it can increase to 15% to 30% when a first degree relative has the diagnoses. In hereditary predisposition cancer syndrome like the Lynch syndrome it can grow up to 80% [2].

Polyp burden in Lynch syndrome patients ascertained via multigene panel testing.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 596-596
Author(s):  
Maegan Roberts ◽  
Megan L. Marshall ◽  
Erica M Webb ◽  
Anna K. McGill ◽  
Lisa R. Susswein ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Adenomatous Polyps ◽  
Published Data ◽  
Colon Polyps ◽  
Testing Methods ◽  
Cancer Syndrome ◽  
Panel Testing ◽  
History Of ◽  
Pathology Reports

596 Background: Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer (HNPCC), is a hereditary colorectal cancer syndrome thought to present with few or no polyps. It has been suggested that the majority of LS patients with colon polyps will develop 1-9 cumulative adenomatous polyps in their lifetime, while approximately 10% will develop ≥10. Our aim was to describe polyp burden in a cohort of LS patients who were ascertained via multi-gene cancer panel testing. Methods: We retrospectively reviewed the personal history for all individuals with a pathogenic or likely pathogenic variant (collectively, PV) in MLH1, MSH2 (including 3’ EPCAM deletions), MSH6, or PMS2. Individuals with more than one PV in a LS-associated or other gene were excluded. All polyp data was obtained from provided test requisition forms and/or pathology reports. Results: A total of 131 individuals reported to have colon polyps were molecularly confirmed as having LS. Of these individuals, 55% (72/131) reported a history of colorectal cancer. Overall, polyp burden was reported as follows: 83% (109/131) with 1-10 polyps, 13% (17/131) with 10-19 polyps, and 4% (5/131) with 20-50 polyps. Of the 5 individuals reporting 20-50 polyps, the average was 31.2 polyps (range 21-50). Adenomatous pathology was reported for one or more polyps in 69% (91/131) of individuals. When limited to those with adenomatous polyps, 85% (77/91) reported 1-10 polyps, 11% (10/91) reported 10-19 polyps, and 4% (4/91) reported 20-50 polyps. When breaking down by presence and absence of colorectal cancer, 18% (13/72) and 15% (9/59), respectively, reported a polyp burden ≥10. Overall, 17% (22/131) of all LS patients reported ≥10 polyps. Conclusions: Similar to previously published data, the majority of LS patients with colon polyps report a polyp burden of < 10. However, our data suggest that the proportion of LS patients with a polyp burden of ≥10 may be higher than previously reported (17% vs. 10%) stressing the importance of including the LS-associated genes for these patients. While LS has historically been referred to as a “non-polyposis” syndrome, a subset of patients actually present with an attenuated polyposis-like phenotype.

scholarly journals Mathematical Modeling of Multiple Pathways in Colorectal Carcinogenesis using Dynamical Systems with Kronecker Structure

2020 ◽  
Author(s):  
Saskia Haupt ◽  
Alexander Zeilmann ◽  
Aysel Ahadova ◽  
Magnus von Knebel Doeberitz ◽  
Matthias Kloor ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dynamical System ◽  
Lynch Syndrome ◽  
Gene Mutation ◽  
Colorectal Carcinogenesis ◽  
Tumor Evolution ◽  
Cancer Syndrome ◽  
Kronecker Sum ◽  
The Matrix ◽  
Medical Hypothesis

AbstractLike many other tumors, colorectal cancers develop through multiple pathways containing different driver mutations. This is also true for colorectal carcinogenesis in Lynch syndrome, the most common inherited colorectal cancer syndrome. However, a comprehensive understanding of Lynch syndrome tumor evolution which allows for tailored clinical treatment and even prevention is still lacking.We suggest a linear autonomous dynamical system modeling the evolution of the different pathways. Starting with the gene mutation graphs of the driver genes, we formulate three key assumptions about how these different mutations might be combined. This approach leads to a dynamical system that is built by the Kronecker sum of the adjacency matrices of the gene mutation graphs. This Kronecker structure makes the dynamical system amenable to a thorough mathematical analysis and medical interpretation, even if the number of incorporated genes or possible mutation states is increased.For the case that some of the mathematical key assumptions are not satisfied, we explain possible extensions to our model. Additionally, improved bio-medical measurements or novel medical insights can be integrated into the model in a straightforward manner, as all parameters in the model have a biological interpretation. Modifications of the model are able to account for other forms of colorectal carcinogenesis, such as Lynch-like and familial adenomatous polyposis cases.Graphical Abstract:From the Medical Hypothesis Over the Modeling Approach To the Mathematical Structure.The medical hypothesis of multiple pathways in carcinogenesis is widely known for various types of cancer. Left: We present a model for this phenomenon at the example of Lynch syndrome, the most common inherited colorectal cancer syndrome, with specific key driver events in the MMR genes, CTNNB1, APC, KRAS and TP53. Middle: This current medical understanding of carcinogenesis is translated into a mathematical model using a specific dynamical system, which can be represented by a graph structure, where each vertex in the graph represents a genotypic state and the edges correspond to the transition probabilities between those states. Starting with all colonic crypts in the state of all genes being wild-type and a single MMR germline mutation due to Lynch syndrome, we are interested in the distribution of the crypts among the graph at different ages of the patient in order to obtain estimates for the number of crypts in specific states, e.g. adenomatous or cancerous states. Right: The underlying matrix of the dynamical system makes use of the Kronecker sum and product. It is a sparse upper triangular matrix accounting for the assumption that mutations cannot be reverted. This allows fast numerical solving by using the matrix exponential. Each nonzero entry of the matrix represents a connection between genotypic states in the graph.

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