scholarly journals Report of a Novel Mutation inMLH1Gene in a Hispanic Family from Puerto Rico Fulfilling Classic Amsterdam Criteria for Lynch Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Juan M. Marqués-Lespier ◽  
Yaritza Diaz-Algorri ◽  
Maria Gonzalez-Pons ◽  
Marcia Cruz-Correa
Keyword(s):  
Colorectal Cancer ◽  
Puerto Rico ◽  
Lynch Syndrome ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Limited Information ◽  
Protein Coding ◽  
Genetic Sequencing ◽  
Amsterdam Criteria ◽  
Hispanic Family

In Puerto Rico, colorectal cancer (CRC) represents the second leading cause of cancer in men and women. Familial CRC accounts for 10–15% of the total CRC cases, while Lynch syndrome accounts for approximately 2–4% of cases. Limited information is available about the prevalence, clinical manifestations, and genetic mutations of hereditary CRC in US Hispanic individuals. In this paper we report a novel mutation in thehMLH1gene in a Puerto Rican Hispanic family with Lynch syndrome recruited through the Puerto Rico Familial Colorectal Cancer Registry (PURIFICAR). Our proband was identified by applying Amsterdam and Bethesda criteria for Lynch syndrome, analysis of protein expression by immunohistochemistry, and genetic sequencing of the mismatch repair genes. A novel mutation at c.2044_2045 inhMLH1consisting of the deletion of two consecutive nucleotides (AT) at exon 18 was identified. This deletion causes a frameshift in the protein coding sequence at p.682 resulting in premature termination and a truncated MLH1 protein. To our knowledge, this mutation has not been previously reported in the literature. The detection of this novel mutation inMLH1further emphasizes the need for genetic testing in at-risk patients for hereditary CRC from various ethnic and racial backgrounds.

scholarly journals Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abram Bunya Kamiza ◽  
Wen-Chang Wang ◽  
Jeng-Fu You ◽  
Reiping Tang ◽  
Huei-Tzu Chien ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cumulative Risk ◽  
Germline Mutations ◽  
Han Chinese ◽  
Chinese Patients ◽  
Mutation Carriers ◽  
Amsterdam Criteria ◽  
Cumulative Risks ◽  
Age And Sex

AbstractPatients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%–89.9%) and 76.7% (95% CI = 37.2%–99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%–57.7%) and 49.3% (95% CI = 21.9%–84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

scholarly journals Performance of tumor testing for Lynch syndrome identification in patients with colorectal cancer: A retrospective single-center study

2018 ◽  
Vol 105 (1) ◽  
pp. 76-83 ◽  
Author(s):  
Stefano Signoroni ◽  
Maria Grazia Tibiletti ◽  
Maria Teresa Ricci ◽  
Massimo Milione ◽  
Federica Perrone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Characteristic Curve ◽  
Age At Onset ◽  
Area Under The Curve ◽  
Single Center ◽  
Germline Variants ◽  
Amsterdam Criteria ◽  
Clinicopathologic Parameters ◽  
Msi Analysis

Objective: To investigate the performance of tumor testing approaches in the identification of Lynch syndrome (LS) in a single-center cohort of people with colorectal cancer (CRC). Methods: A retrospective analysis of data stored in a dedicated database was carried out to identify patients with CRC suspected for LS who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, between 1999 and 2014. The sensitivity and specificity of immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis (alone or combined) were calculated with respect to the presence of causative MMR germline variants. Results: A total of 683 patients with CRC suspected for LS were identified. IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features. Univariate and multivariate analysis revealed a significant correlation of pathogenic MMR germline variants with all clinicopathologic features including Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset, stage, and grade. The highest odds ratio values were observed for IHC and MSI (17.1 and 8.8, respectively). The receiver operating characteristic curve and area under the curve values demonstrated that IHC alone or combined with other clinicopathologic parameters was an excellent test for LS identification. Conclusions: This study confirms the effectiveness of tumor testing to identify LS among patients with CRC. Although IHC and MSI analysis were similarly effective, IHC could be a better strategy for LS identification as it is less expensive and more feasible.

Implementation of Universal Colorectal Cancer Screening for Lynch Syndrome in Hispanics Living in Puerto Rico

2020 ◽  
Author(s):  
Isabel Sierra ◽  
Julyann Pérez-Mayoral ◽  
Kathia Rosado ◽  
Valerie Maldonado ◽  
Kimberly Alicea-Zambrana ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Puerto Rico ◽  
Cancer Screening ◽  
Lynch Syndrome ◽  
Colorectal Cancer Screening

scholarly journals Differential diagnosis of small bowel occlusions

2009 ◽  
Vol 3 (2) ◽  
pp. 81-87
Author(s):  
Paolo Ghiringhelli
Keyword(s):  
Colorectal Cancer ◽  
Differential Diagnosis ◽  
Lynch Syndrome ◽  
Hereditary Nonpolyposis Colorectal Cancer ◽  
Autosomal Dominant ◽  
Age At Onset ◽  
Clinical Manifestations ◽  
Early Age ◽  
Increased Risk ◽  
Hereditary Nonpolyposis

Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, and microsatellite instability (MSI). Patients with Lynch syndrome have a markedly increased risk of colorectal cancer. We report a case of a 28-year-old male with Lynch syndrome; the case allows to describe clinical manifestations and diagnostic criteria of this syndrome, and to underline the importance of genetics in the diagnosis of this disease.

scholarly journals Lynch syndrome I: A case report

2008 ◽  
Vol 61 (1-2) ◽  
pp. 79-82
Author(s):  
Vesna Zivkovic ◽  
Vuka Katic ◽  
Jasmina Gligorijevic ◽  
Zlatibor Andjelkovic ◽  
Aleksandar Petrovic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Case Report ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Clinical Stage ◽  
Family Members ◽  
Advanced Rectal Cancer ◽  
Degree Relative ◽  
Mmr Genes ◽  
Amsterdam Criteria

Introduction. Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndromes J and II, accounts for about 5-8% of colorectal cancers. Lynch syndrome I is an autosomal domi?nant inherited disorder characterized by early onset of colorectal cancer, predominance of proximal and multiple tumors, and microsatellite instability. In order to identify HNPCC, the international "Amsterdam criteria" have been used. Case report. The proband was a 40-year-old male who was admitted to hospital with a diagnosis of advanced rectal cancer. Left colectomy was carried out. A histopathologic diagnosis of poorly differentiated adenocarcinoma of clinical stage Dukes C was made. The family talking was done and it was revealed that the pro-band had five family members (one of first degree relative) with colorectal cancer, and two successive generations affected. All malignancy were diagnosed before 45 years of age. In one family member, metachronous transverse cancer was revealed 12 years after surgery for cecal adenocarcinoma. Discussion and conclusion. The main molecular cause for HNPCC is constitutional mutation in one of the mismatch repair (MMR) genes that regulate the excision of errors occurring during DNA replication. The most often are mutations of MLHI and MSH2 genes, and microsatellite instability is present in about 90-95% HNPCC. In this report, we present a case of an HNPCC patient who met the Amsterdam criteria for Lynch syndrome I. Family members that fulfill the Amsterdam criteria should be investigated for mutation in MMR genes. The genetic tests are not routinely available, so colonoscopic screening of all asymptomatic family members older than 25 has been recommended.

scholarly journals Clinical, anamnestic, molecular and genetic criteria for Lynch syndrome

2019 ◽  
Vol 6 (4) ◽  
pp. 38-46
Author(s):  
A. V. Semyanikhina ◽  
N. I. Pospekhova ◽  
M. G. Filippova ◽  
D. A. Golovina ◽  
A. O. Rasulov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Expression Patterns ◽  
Clinical Criteria ◽  
Mmr Genes ◽  
Leading Role ◽  
Amsterdam Criteria ◽  
Colorectal Cancer Patients ◽  
Mmr Proteins

Lynch syndrome is the most common cancer-prone syndrome associated with a high risk of colorectal cancer (CRC), neoplasms of the upper gastrointestinal system, the urinary tract, the female reproductive system, brain tumours and others. The only known form of hereditary endometrial cancer is also diagnosed as part of Lynch syndrome. One or more pathogenic germline mutations in one of the mismatch repair (MMR) genes are the cause of Lynch syndrome. Mapping of MMR genes and the discovery of microsatellite instability (MSI) have given rise to the possibility of using these clue characteristics of the pathogenic process for the elaboration of a screening test for Lynch syndrome. Being highly accurate and superior to all previously developed clinical criteria and guidelines, MSI-testing along with the assessment of the expression patterns of MMR proteins by immunohistochemistry has taken the leading role in the early diagnosis of Lynch syndrome. This article focuses on a brief review about the main evolutionary stages of clinical, anamnestic, molecular and genetic criteria for Lynch syndrome together with the results of our own research on the accuracy of the Amsterdam criteria, the Bethesda guidelines and MSI-diagnostics in the determination of the indications for MMR-genotyping in colorectal cancer patients suspected for Lynch syndrome.

scholarly journals Phenotypic Heterogeneity by Germline Mismatch Repair Gene Defect in Lynch Syndrome Patients

2016 ◽  
Vol 29 (10) ◽  
pp. 587
Author(s):  
Jorge Hernâni-Eusébio ◽  
Elisabete Barbosa
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Statistical Significance ◽  
Phenotypic Correlation ◽  
Mismatch Repair Gene ◽  
Small Data ◽  
Repair Gene ◽  
Amsterdam Criteria

Introduction: Lynch syndrome is the most common form of hereditary colorectal cancer, being also responsible for endometrial and other types of cancers. It is associated with germline mutations in DNA mismatch repair genes and microsatellite instability. MLH1 and MSH2 mutations have a “classical” Lynch syndrome phenotype, with MSH2 having a higher association with extracolonic cancer. MSH6 and PMS2 mutations have an atypical phenotype. Clinical expression is heterogeneous, with correlation between mismatch repair mutated gene and phenotypic patterns.Material and Methods: We retrospectively analyzed data from patients fulfilling Amsterdam criteria or having mismatch repair gene mutations, between September 2012 and October 2015.Results: We identified 28 patients. Seventeen had colorectal cancer with right colon predominance. Five developed endometrial cancer (median age of diagnosis – 53), with no MSH6 mutations. Five developed other cancers. All mutated mismatch repair cases studied had microsatellite instability.Discussion: Most cases had MSH2 mutations despite MLH1 being described in the literature as the most frequently mutated. Interestingly, colorectal cancer patients showed no tendency for high inflammatory infiltrate. Despite the high incidence of synchronous and metachronous tumours, most patients underwent a partial colectomy. Prophylactic hysterectomy and adnexectomy was performed in menopausal/perimenopausal patients.Conclusion: A standardized registration of patient’s data may lead to better management and knowledge about Lynch syndrome. Use of Bethesda Guidelines might identify new cases non-identified by Amsterdam criteria. Microsatellite instability analysis must be performed in a much larger scale. The genotypic/phenotypic correlation described in the literature was not verified in our study with statistical significance, perhaps due to small data sample and insufficient clinical registration.

Presence of familial colorectal cancer type X in families fulfilling Amsterdam criteria for Lynch syndrome in southern Brazil.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12546-e12546
Author(s):  
Patricia Ashton-Prolla ◽  
Naye Balzan Schneider ◽  
Cristina Netto ◽  
Silvia Liliana Cossio ◽  
Patricia Koehler-Santos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Cancer Genetics ◽  
Hereditary Colorectal Cancer ◽  
Cancer Type ◽  
Southern Brazil ◽  
Familial Colorectal Cancer ◽  
Nuclear Expression ◽  
Amsterdam Criteria ◽  
Mmr Deficiency

e12546 Background: The clinical diagnosis of Lynch syndrome is usually established when a family fulfills the Amsterdam Criteria, and confirmed by identification of MMR deficiency and/or germline mutations in one of the MMR genes. In a subset of families with Amsterdam criteria, no evidence of DNA mismatch repair deficiency can be identified and this clinical entity has been designated “Familial Colorectal Cancer Type X (FCCTX)”. Methods: The prevalence of MMR deficiency was assessed in a group of 25 individuals with colorectal or endometrial cancer from 20 families fulfilling Amsterdam criteria in Southern Brazil. MMR deficiency was assessed by IHC testing using a panel of antibodies against MSH2, MLH1, MSH6, and PMS2. In cases showing loss of nuclear expression of MLH1, presence of the BRAF p.V600E mutation and microsatellite instability were assessed in the tumor. Results: Fourteen of the 20 families studied fulfilled Amsterdam II criteria. MMR deficiency was identified in the tumor of 11 index cases and in the remaining 9, nuclear expression of all four MMR proteins was normal, suggesting the diagnosis of FCCTX. This FCCTX phenotype was observed in both Amsterdam I and Amsterdam II families. CRC with MMR-deficiency was diagnosed at an earlier age (41.2 years) than CRC showing MMR proficiency (47.2 years), although the difference did not reach significance. Conclusions: FCCTX is a frequent differential diagnosis in hereditary colorectal cancer in patients presenting to high risk cancer genetics clinics in Southern Brazil and further molecular characterization of hereditary colorectal cancer families with these features is warranted.

scholarly journals HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (LYNCH SYNDROME) PADA WANITA UMUR 16 TAHUN

2011 ◽  
Vol 35 (2) ◽  
pp. 172
Author(s):  
Asril Zahari ◽  
Sudiyatmo Sudiyatmo
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Abdominal Mass ◽  
Lower Abdominal Pain ◽  
Hepatic Flexure ◽  
Amsterdam Criteria ◽  
Genetic Abnormalities ◽  
Similar Disease ◽  
History Of

AbstrakKanker kolorektal menduduki peringkat ketiga jenis kanker yang paling sering terjadi di dunia. Sekitar 3% kasus kanker kolorektal merupakan jenis hereditary non polyposis colorectal cancer (HNPCC)/Lynch syndrome, yang sering muncul pada usia muda. Dilaporkan satu kasus di rumah sakit Dr. M. Djamil Padang, wanita berumur 16 tahun dengan keluhan nyeri perut kanan bawah. Didapatkan riwayat penyakit serupa pada kakek, bibi pasien dan enam anggota keluarga yang lain. Pada pemeriksaan fisik abdomen teraba massa dengan konsistensi keras dan terfiksir. Pada kolonoskopi dan biopsi ditemukan tumor jenis adenocarcinoma colon moderatly differentiated di fleksura hepatika dan polip di kolon sigmoid. Berdasarkan kriteria Amsterdam pasien didiagnosa Lynch syndrome. Pada Pasien dilakukan subtotal kolektomi, anastomose ileorectal dan kemoterapi ajuvan. Identifikasi genetik sedang dikerjakan untuk melihat adanya kelainan genetik pada pasien. Pasien melakukan skrining berkala untuk mencegah kanker HNPCC jenis yang lain.Kata kunci : Hereditary non polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, skrining.AbstractCarcinoma colorectal is the third most common type of cancer that occurs in the world. About 2% -3% of cases of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome, which often appear at a young age. Amsterdam and Bethesda criteria have been used to identify patients with Lynch syndrome.one case was reported at the Dr. M. Djamil Padang hospital, a 16-year-old girl with right lower abdominal pain. Obtained a history of similar disease in grandparents, aunts and six other family members. On physical examination found palpable fixed abdominal mass with hard consistency in the lower right abdomen. At colonoscopy and biopsy found a moderatly differentiated adenocarcinoma colon type at the hepatic flexure and the sigmoid colon polyp. Based on the Amsterdam criteria, patients diagnosed with HNPCC/Lynch syndrome. Patients treated with subtotal colectomy, ileorectal anastomose and adjuvant chemotherapy.LAPORAN KASUS173Genetic identification is underway to see any genetic abnormalities. Patients be screened regularly to prevent other types of cancer HNPCC.Key word : Hereditary non-polyposis colorectal cancer, Lynch syndrome, Microsatellite instability, screening.

Sign in / Sign up

Export Citation Format

Share Document