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Understanding Lynch Syndrome: Genetic and Molecular Insights – Mutations
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category-lynch-syndrome tag-chemoprevention tag-dna-mmr tag-entogenic-therapy tag-genetic-consultation tag-genetic-mutations-and-colon-cancer tag-hnpcc tag-lynch-syndrome tag-msi tag-preventive-surgery tag-til" itemtype="https://schema.org/CreativeWork" itemscope> <div class="inside-article"> <div class="featured-image page-header-image-single "> <img width="1200" height="628" src="https://mutation.blog/archive/wp-content/uploads/2024/11/banner-01-4-1-min-scaled-e1731663344101.jpg" class="attachment-full size-full" alt="" itemprop="image" decoding="async" fetchpriority="high" /> </div> <header class="entry-header"> <h1 class="entry-title" itemprop="headline">Understanding Lynch Syndrome: Genetic and Molecular Insights</h1> <div class="entry-meta"> <span class="posted-on"><time class="entry-date published" datetime="2024-11-15T15:05:58+05:30" itemprop="datePublished">November 15, 2024</time></span> <span class="byline">by <span class="author vcard" itemprop="author" itemtype="https://schema.org/Person" itemscope><a class="url fn n" href="https://mutation.blog/archive/author/mutation/" title="View all posts by mutation" rel="author" itemprop="url"><span class="author-name" itemprop="name">mutation</span></a></span></span> </div> </header> <div class="entry-content" itemprop="text"> <h4><b>Introduction</b></h4> <p><span style="font-weight: 400;">Lynch syndrome, or Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is a frequent hereditary cancer predisposition with a strong relationship with CRC and other malignancies. Although COLO-Lanschow colorectal cancer and Lynch syndrome are not occasional, they are seen with early age onset and are correlated with numerous other cancers, including endometrial, ovarian, and gastric. Lynch syndrome is a polyposis condition that originates from hereditary mutations of DNA mismatch repair genes that culminate in microsatellite instability. Understanding the genetic and molecular profile of Lynch syndrome to identify patients that may be susceptible to developing Lynch syndrome-related cancers is critical in screening, prevention, and management of the condition and hence is heavily researched in the oncology fraternity.</span></p> <h4><b>Genetic Features of Lynch Syndrome</b></h4> <p><span style="font-weight: 400;">Lynch syndrome is an inherited variant involving germline mutations of mismatch repair genes, with MLH1, MSH2, MSH6, and PMS2 being the most common. These genes are involved in the repair of errors that would have occurred during the process of DNA replication. When any of these genes are mutated, the MMR system is compromised, making way for the stewing of mutations all over the body. This buildup usually results in the growth of cancer, especially where new cells are quickly formed, as in the colon.</span></p> <p><span style="font-weight: 400;">The mutations may also be inherited in an autosomal dominant fashion; this means that inheriting one altered gene from either parent can put a person at risk of Lynch syndrome. The penetrance of these mutations is also high; indeed, the lifetime risk of colorectal cancer may be up to 80% in individuals with definite germline mutations in MLH1 and MSH2. The risk for other kinds of cancer, including endometrial cancer, is raised dramatically as well.</span></p> <h4><b>Nucleotide Signatures: Microsatellite Instability</b></h4> <p><span style="font-weight: 400;">Microsatellite instability is a condition of genomic instability due to mutations in mismatch repair. Microsatellites are tandem repeats of the 1–6 bases, which are normally subject to slippage during replication. In normal cells, these kinds of mistakes get repaired because of the existence of a system known as the MMR system. If the cells are deficient for MMR, these errors are not corrected, and hence MSI is observed.</span></p> <p><span style="font-weight: 400;">MSI can be found in about 15% of all colorectal cancers, although it is most closely associated with Lynch syndrome, which occurs in nearly all patients. Based on the degree of instability, MSI can be classified into three groups. MSI is also characterized by MSSI as high-frequency MSI, low-frequency MSI, and microsatellite stable. Given the less aggressive behavior and sensitivity to some chemotherapeutic agents, MSI-H tumors stand apart; MSI seems to turn into a useful factor for prognosis in CRC.</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Yearwise Publication Trend on <b>“<a href="https://mutation.blog/publication-trends/index/lynch syndrome" target="_blank" title="lynch syndrome - yearwise publication trends">lynch syndrome</a>”</b></h2> </div> </div><div class="results-container"><div class="chart-block" style="padding:15px;"> <div class="left"> <div id="results" class="results"></div> </div> <div class="right"> <div class="chart-container"><canvas id="publicationChart"></canvas></div> </div> <div class="keywordsdiv"> <div style="text-align:center;"><b>Find publication trends on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-stats"></span> </div> </div></div></div><div class="inside-article"><style> table { margin: 0 0 1.5em; 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'NA' : count; tableHTML += ` <tr> <td>${year}</td> <td>${displayCount}</td> </tr> `; }); tableHTML += '</table></div>'; resultsContainer.innerHTML = tableHTML; } function displayLineChart(statistics) { var years = Object.keys(statistics); var counts = Object.values(statistics); var ctx = document.getElementById('publicationChart').getContext('2d'); // Destroy existing chart instance if it exists if (chart !== null) { chart.destroy(); } // Create a new chart instance chart = new Chart(ctx, { type: 'line', data: { labels: years, datasets: [{ label: 'Publication Counts', data: counts, fill: false, borderColor: 'rgba(75, 192, 192, 1)', tension: 0.1 }] }, options: { scales: { y: { beginAtZero: true } }, plugins: { legend: { display: true, position: 'top' } } } }); } function displayKeywordStats(keywords) { var resultsContainer = document.getElementById('keyword-stats'); resultsContainer.innerHTML = ''; if (!keywords || keywords.length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var keywordHTML = ''; keywords.forEach((key, index) => { let key_replace = key.replace(/ /g, '-'); key_replace = key_replace.toLowerCase(); keywordHTML += `<a href="https://mutation.blog/publication-trends/index/${key_replace}" target="_blank" title="${key} - yearwise publication trends">${key}</a>`; if (index < keywords.length - 1) { keywordHTML += ', '; } }); resultsContainer.innerHTML = keywordHTML; } // Call the function with the PHP data var statistics = { "2014": 114, "2015": 98, "2016": 115, "2017": 138, "2018": 113, "2019": 178, "2020": 260, "2021": 271, "2022": 288, "2023": 493, "2024": 230 }; var keywordsArray = ["Lynch Syndrome","HNPCC","DNA MMR","MSI","Genetic mutations and Colon cancer","TIL","Entogenic therapy","Genetic consultation","Preventive surgery","Chemoprevention"]; displayResults(statistics); displayLineChart(statistics); displayKeywordStats(keywordsArray); </script></p> <h4><b>Pathogenesis and Tumor Characteristics</b></h4> <p><span style="font-weight: 400;">Thus, the molecular action of Lynch syndrome-associated cancers is still manifestly other than the adenoma-carcinoma sequence that occurs in the majority of sporadic CRCs. In Lynch syndrome, colorectal cancer develops after the loss of function of one of the MMR genes and subsequent genetic instability in other important genes concerning cell proliferation and programmed cell death. The HNPCC cancers mainly develop in the proximal colon, whereas the sporadic CRCs are seen in the distal colon. Lynch syndrome tumors are seen to be of poor differentiation, mucinous type, and high TILs, which is a measure of immune reaction to tumors.</span></p> <p><span style="font-weight: 400;">It is also conventional for Lynch syndrome tumors to exhibit mutations in the BAX gene or the TGFBRII gene. The BAX gene is implicated in apoptosis, and its aberration makes the cancer cells resistant to apoptosis and thus survive longer. TGFBRII belongs to the class of receptor type I that is implicated in the TGF-beta signaling that controls cell development and differentiation. There are indications that mRNA expression of TGFBRII is prognostic for better outcomes in LS patients, as such tumors are less malignant.</span></p> <h4><b>Diagnosis and Screening</b></h4> <p><span style="font-weight: 400;">Due to the high risk of cervical cancer among Lynch syndrome patients, it is crucial to diagnose the disease at an earlier stage and conduct regular screenings. Lynch syndrome is usually diagnosed with the help of criteria that include family history, clinical characteristics, and molecular testing. Lynch syndrome is established clinically by the Amsterdam Criteria and the revised Bethesda Guidelines to delineate people who require further testing. Molecular testing itself includes the evaluation of MSI and IHC of tumor tissue for MMR protein levels. Lack of expression of any of these proteins indicates that there is a defective gene of MMR associated. If MSI or loss of MMR protein expression is positive, then germline genetic testing is done along with the diagnosis of Lynch syndrome.</span></p> <p><span style="font-weight: 400;">If there is a confirmed mutation in a family, then this can be followed up by predictive genetic testing of the other at-risk family members. It makes it possible to define those patients who might require additional monitoring and preventive measures, including, for instance, a colonoscopy at an earlier age than recommended for other individuals.</span></p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Recent Publications on <b>“<a href="https://mutation.blog/recent-publications/index/lynch syndrome" target="_blank" rel="noopener" title="lynch syndrome - yearwise publication list">lynch syndrome</a>”</b></h2> </div> </div> <div class="pb-main"><div class="article-scroll"><div id="results_recent" class="results"></div></div><div class="keywordsdiv" style="margin: 0px 15px;margin-top:20px;"> <div style="text-align:center;"><b>Find publications on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-papers"></span> </div></div></div><div class="inside-article"> <style> .pb-main{ border: solid 1px #ccc; border-top: none; margin-bottom: 20px; padding-bottom: 25px; background:#fff; } .author-main { border: solid 1px #ccc; border-top: none; margin-bottom: 20px; padding-bottom: 25px; background:#fff; } .publication-block { padding: 10px; margin-bottom: 10px; background-color: #f9f9f9; text-align: left; background: #FFF; border-bottom: solid 1px #ccc; margin-left: 15px; margin-right: 15px; } .publication-block h3 { margin: 0 0 10px; color: #000!important; } .publication-block a { font-size: 16px !important; line-height: 1em; font-weight: 600; text-transform: none; color: #000; padding: 0px; } .publication-block a:hover{ color: #227cdc; text-decoration:underline; } .article-scroll { max-height: 445px; overflow-y: auto; overflow-x: hidden; } ::-webkit-scrollbar-track { -webkit-box-shadow: inset 0 0 6px rgba(0,0,0,0.3); background-color: #efefef; border-radius:30px; } ::-webkit-scrollbar { width: 6px; background-color: #efefef; border-radius:30px; } ::-webkit-scrollbar-thumb { background-color: #ababab; border-radius:30px; } .publication-block p { margin-bottom: .5em; font-size: 15px; color: #000; } h3 { font-size: 18px !important; margin-bottom: 20px; line-height: 1.2em; font-weight: 600; text-transform: none; } a { padding: 5px; color: #a71c49; } #keyword-papers{ margin-top: 20px; text-align: center; } </style> <script> function decodeString(str) { str = str.replace(/\\'/g, "'"); str = str.replace(/\\'/g, "'"); str = str.replace(/\\'/g, "'"); return str; } function displayResults_recent(papers) { var resultsContainer = document.getElementById('results_recent'); if (!papers || papers.length === 0) { resultsContainer.innerHTML = '<p>No recent publications found.</p>'; return; } papers.forEach(paper => { var publicationBlock = document.createElement('div'); publicationBlock.className = 'publication-block'; var title_de = decodeString(paper.title); var publicationHTML = ` <div style="margin-bottom: 10px;line-height: 24px;"><a href="${paper.url}" target="_blank" title="${title_de}">${title_de}</a></div> <p><strong>Issue Release:</strong> ${paper.publishedDate}</p> `; publicationBlock.innerHTML = publicationHTML; resultsContainer.appendChild(publicationBlock); }); } function displayKeywordPapers(keywords) { var resultsContainer = document.getElementById('keyword-papers'); resultsContainer.innerHTML = ''; if (!keywords || keywords.length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var keywordHTML = ''; keywords.forEach((key, index) => { let key_replace = key.replace(/ /g, '-'); key_replace = key_replace.toLowerCase(); keywordHTML += `<a href="https://mutation.blog/recent-publications/index/${key_replace}" target="_blank" title="${key} - publication list">${key}</a>`; if (index < keywords.length - 1) { keywordHTML += ', '; } }); resultsContainer.innerHTML = keywordHTML; } // Call the function with the PHP data var recent_papers = [ { "title": "The impact of hysterectomy on subsequent colonoscopy in women with Lynch Syndrome.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38946231", "publishedDate": "2024" }, { "title": "EPM2AIP1 Immunohistochemistry Is Inadequate as A Surrogate Marker for MLH1 Promoter Hypermethylation Testing in Colorectal Cancer.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38945374", "publishedDate": "2024" }, { "title": "Detection of a major Lynch Syndrome-causing MLH1 founder variant in a large-scale genotyped cohort.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38847920", "publishedDate": "2024" }, { "title": "Modifiable risk factors for cancer among people with lynch syndrome: an international, cross-sectional survey.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38877502", "publishedDate": "2024" }, { "title": "Use of PSMA PET\/CT to detect prostate cancer metastatic to a preexisting thyroid nodule.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38879699", "publishedDate": "2024" }, { "title": "Misclassification of a frequent variant from PMS2CL pseudogene as a PMS2 loss of function variant in Brazilian patients.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38900223", "publishedDate": "2024" }, { "title": "A REVIEW TO HONOR THE HISTORICAL CONTRIBUTIONS OF PAULINE GROSS, ALDRED WARTHIN, AND HENRY LYNCH IN THE DESCRIPTION AND RECOGNITION OF INHERITANCE IN COLORECTAL CANCER.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38958348", "publishedDate": "2024" }, { "title": "Complications of colonoscopy surveillance of patients with Lynch syndrome - 33 years of follow up.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/39102097", "publishedDate": "2024" }, { "title": "Universal Lynch Syndrome Screening in Colorectal Cancer: A 5-Year Experience of a Portuguese Pathology Department.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/39105266", "publishedDate": "2024" }, { "title": "Routine use of MSI testing in colorectal cancer using a proposed algorithm.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38873700", "publishedDate": "2024" }, { "title": "Novel Cancer Prevention Strategies in Individuals With Hereditary Cancer Syndromes: Focus on , , and Lynch Syndrome.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38913968", "publishedDate": "2024" }, { "title": "Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38915709", "publishedDate": "2024" }, { "title": "Genomic landscape of diploid and aneuploid microsatellite stable early onset colorectal cancer.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38654044", "publishedDate": "2024" }, { "title": "Impact of hormonal contraception on endometrial histology in patients with Lynch syndrome, a retrospective pilot study.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38687437", "publishedDate": "2024" }, { "title": "Paeoniae radix rubra:A review of ethnopharmacology, phytochemistry, pharmacological activities, therapeutic mechanism for blood stasis syndrome, and quality control.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38850115", "publishedDate": "2024" }, { "title": "Diaphragmatic clear cell carcinoma with Lynch syndrome after surgery for atypical endometrial hyperplasia and ovarian endometriosis: A case report.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38826696", "publishedDate": "2024" }, { "title": "Germline Testing identifies Pathogenic\/Likely Pathogenic Variants in Patients with Pancreatic Neuroendocrine Tumors.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38662083", "publishedDate": "2024" }, { "title": "Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated \\\\\\\"Big Bang\\\\\\\" pathway to CRC in three of the four Lynch syndromes.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38741120", "publishedDate": "2024" }, { "title": "Unveiling pembrolizumab effectiveness in diverse subtypes of MSI-high endometrial cancers.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38725237", "publishedDate": "2024" }, { "title": "Outcomes and the effect of PGT-M in women with hormone-related hereditary tumor syndrome.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38800375", "publishedDate": "2024" } ]; var keywordsArray = ["Lynch Syndrome","HNPCC","DNA MMR","MSI","Genetic mutations and Colon cancer","TIL","Entogenic therapy","Genetic consultation","Preventive surgery","Chemoprevention"]; displayResults_recent(recent_papers); displayKeywordPapers(keywordsArray); // function stripslashes(str) { // if (typeof str === 'string') { // return str.replace(/\/g, ''); // } // } </script></p> <h4><b>Management and Prevention</b></h4> <p><span style="font-weight: 400;">Monitoring of Lynch syndrome involves screening for the development of colorectal and other related malignancies and has specific indications for surgical prophylaxis. Colonoscopy thus forms the mainstay of cancer prevention in Lynch syndrome because histologically adenomatous polyps can be identified endoscopically and surgically removed at a curable stage. The frequency for this examination is not fixed, but colonoscopy should be done every 1 to 2 years, starting from the age of 20 to 25, or 2 to 5 years before the youngest age of colorectal cancer in the family.</span></p> <p><span style="font-weight: 400;">Women with Lynch syndrome should also be recommended to undergo screening tests for very frequent endometrial and ovarian cancers. In cases where a strong family history is noted for these cancers, a prophylactic hysterectomy and oophorectomy may be considered following fecundity. Another area of research in Lynch syndrome is that of chemoprevention. Results of some studies indicate that aspirin intake reduces the incidence of CRC in LS patients, but the dosage and duration of aspirin therapy are highly speculative. The NSAIDs have also been given, although the effectiveness and the possible side effects on cancer patients have not spurred further research.</span></p> <h4><b>Genetic Counseling and Family Planning</b></h4> <p><span style="font-weight: 400;">Since Lynch syndrome is genetic, genetic counseling as part of its management is mandatory. A genetic counselor is a healthcare professional who can advise individuals and families on the results of genetic tests, the likelihood of getting cancer, and the choice of a mate.</span></p> <p><span style="font-weight: 400;">To reduce the risk of transmission of Lynch Syndrome genes to the next generation, those with the complication and who are willing to conceive may consider PGD and prenatal diagnostic techniques. As for these options, they bring about multiple ethical and emotional questions that should be discussed with the help of a genetic counselor.</span></p> <h4><b>Directions for Lynch Syndrome Research</b></h4> <p><span style="font-weight: 400;">Current research in Lynch syndrome is still ongoing due to the discovery of new research developments in the genetic and molecular foundations of the syndrome, besides research on new and efficient ways of diagnosing, preventing, and treating the syndrome. Due to the technological expansion of next-generation sequencing and other genomic technologies, new genetic mutations that contribute to Lynch syndrome and other related cancer syndromes may be discovered. These findings could help to develop unified mutation panels and individual strategies regarding the risk of cancer development.</span></p> <p><span style="font-weight: 400;">Another important field of investigation is immunotherapy, which, for example, has shown outstanding results in MSI-H tumors. Lynch Syndrome has revealed these therapies to be effective in the treatment of advanced cancers and a new shot of hope for individuals with limited probabilities of treatment.</span></p> <h4><b>Conclusion</b></h4> <p><span style="font-weight: 400;">Lynch syndrome is a complex and, in many aspects, an intricate medical condition that has many implications for the patient and their family as well as for health care practitioners. However, with the success of the genetic and molecular investigation, there are prospects for increased diagnosis, control, and, in the long run, prevention of the cancers related to this syndrome. These results can help the evaluation, diagnosis, and treatment of patients with Lynch syndrome and make progress in the anti-cancer campaign of hereditary cancer.</span></p> <p></p> <h4><b>References</b></h4> <ol> <li>Umar, A., 2004. <a href="https://onlinelibrary.wiley.com/doi/pdf/10.1155/2004/486032">Lynch syndrome (HNPCC) and microsatellite instability.</a> <i>Disease markers</i>, <i>20</i>(4-5), pp.179-180.</li> <li>Lynch, H.T. and Lynch, J.F., 2004. <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3839282/">Lynch syndrome: history and current status. </a><i>Disease markers</i>, <i>20</i>(4-5), p.181.</li> <li>Ribic, C.M., Sargent, D.J., Moore, M.J., Thibodeau, S.N., French, A.J., Goldberg, R.M., Hamilton, S.R., Laurent-Puig, P., Gryfe, R., Shepherd, L.E. and Tu, D., 2003. <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa022289">Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. </a><i>New England Journal of Medicine</i>, <i>349</i>(3), pp.247-257.</li> <li>Greenson, J.K., Bonner, J.D., Ben-Yzhak, O., Cohen, H.I., Miselevich, I., Resnick, M.B., Trougouboff, P., Tomsho, L.D., Kim, E., Low, M. and Almog, R., 2003. <a href="https://journals.lww.com/ajsp/abstract/2003/05000/phenotype_of_microsatellite_unstable_colorectal.1.aspx">Phenotype of microsatellite unstable colorectal carcinomas: well-differentiated and focally mucinous tumors and the absence of dirty necrosis correlate with microsatellite instability</a>. <i>The American journal of surgical pathology</i>, <i>27</i>(5), pp.563-570.</li> <li>Samowitz, W.S., Curtin, K., Neuhausen, S., Schaffer, D. and Slattery, M.L., 2002. <a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/gcc.10125">Prognostic implications of BAX and TGFBRII mutations in colon cancers with microsatellite instability. </a><i>Genes, Chromosomes and Cancer</i>, <i>35</i>(4), pp.368-371.</li> <li>Suraweera, N., Duval, A., Reperant, M., Vaury, C., Furlan, D., Leroy, K., Seruca, R., Iacopetta, B. and Hamelin, R., 2002. <a href="https://www.sciencedirect.com/science/article/abs/pii/S0016508502004523">Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR.</a> <i>Gastroenterology</i>, <i>123</i>(6), pp.1804-1811.</li> <li>Raedle, J., Schaffner, M., Esser, N., Sahm, S., Trojan, J., Kriener, S., Brieger, A., Nier, H., Bockhorn, H., Berg, P.L. and Frick, B., 2002. <a href="http://chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/viewer.html?pdfurl=https%3A%2F%2Fwww.thieme-connect.com%2Fproducts%2Fejournals%2Fpdf%2F10.1055%2Fs-2002-33419.pdf&tabId=1533495707">Frequency of the Amsterdam criteria in a regional German cohort of patients with colorectal cancer.</a> <i>Zeitschrift für Gastroenterologie</i>, <i>40</i>(08), pp.561-568.</li> </ol> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Top Experts on “<b style="color:#000;font-size:22px;">lynch syndrome</b>“</h2> </div> </div><div class="author-main"><div id="results_author"></div><div style="text-align: center;"><a class="register-button" href="https://mutation.blog/expert-search" target="_blank" rel="noopener">Find experts on any field</a></div></div><div class="inside-article" style="background: none;border: none;box-shadow: none;margin-top: -70px;"> <style> .author-block { padding: 15px; 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", "email": "Paul.Goodfellow@osumc.edu", "slug_tail": "p-goodfellow" } }; //console.log(authors_data); displayResults_author(authors_data); var keywordsArray = ["Lynch Syndrome","HNPCC","DNA MMR","MSI","Genetic mutations and Colon cancer","TIL","Entogenic therapy","Genetic consultation","Preventive surgery","Chemoprevention"]; displayKeywordAuthors(keywordsArray); </script></p> </div> <footer class="entry-meta" aria-label="Entry meta"> <span class="cat-links"><span class="gp-icon icon-categories"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M0 112c0-26.51 21.49-48 48-48h110.014a48 48 0 0143.592 27.907l12.349 26.791A16 16 0 00228.486 128H464c26.51 0 48 21.49 48 48v224c0 26.51-21.49 48-48 48H48c-26.51 0-48-21.49-48-48V112z" /></svg></span><span class="screen-reader-text">Categories </span><a href="https://mutation.blog/archive/category/lynch-syndrome/" rel="category tag">Lynch Syndrome</a></span> <span 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