scholarly journals A new mutL homolog 1 c.1896+5G>A germline mutation detected in a Lynch syndrome‐associated lung and gastric double primary cancer patient

2019 ◽  
Vol 7 (8) ◽  
Author(s):  
Xuyuan Chen ◽  
Xiang Li ◽  
Hongsen Liang ◽  
Lichun Wei ◽  
Qiang Cui ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Cancer Patient ◽  
Germline Mutation ◽  
Primary Cancer ◽  
Mutl Homolog 1

scholarly journals A NovelMLH1Initiation Codon Mutation (c.3G>T) in a Large Chinese Lynch Syndrome Family with Different Onset Age and mRNA Expression Level

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yanni Zhang ◽  
Huishuang Chen ◽  
Zhiyu Peng ◽  
Santasree Banerjee ◽  
Wei Li ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Mrna Expression ◽  
Germline Mutation ◽  
Peripheral Blood ◽  
Expression Level ◽  
Onset Age ◽  
Mrna Expression Level ◽  
Increased Risk ◽  
Lynch Syndrome Family ◽  
Codon Mutation

Lynch syndrome is a genetically and clinically heterogeneous disorder; it is caused by a germline mutation in DNA mismatch repair (MMR) genes. Individuals with a heterozygous mutation in MLH1 have an increased risk for developing colorectal cancer. Here we described a 5-generation Chinese Lynch syndrome family with different severity and onset age. A novel heterozygous germline mutation (c.3G>T, p.Met1Ile) inMLH1gene was discovered by next generation sequencing. Our study also revealed by qPCR that the MLH1 mRNA expression in peripheral blood of patients in this family was remarkably lower than that of the unaffected carriers and non-carriers. The research results indicated that the mRNA expression level may provide predictive suggestions of treatment and management for carriers with the initiation codon mutation ofMLH1in this family. Further studies are undertaken in this family as well as other families with Lynch syndrome to interrogate the exact reasons affecting the MLH1 mRNA expression level and whether mRNA expression in peripheral blood could be a significant factor for early diagnosis and surveillance of Lynch syndrome.

scholarly journals PMS2 germline mutation c.943C>T (p.Arg315*)‐induced Lynch syndrome‐associated ovarian cancer

2019 ◽  
Vol 7 (6) ◽  
Author(s):  
Xiaoqing Guo ◽  
Weimin Wu ◽  
Hao Gao ◽  
Xiaofeng Li ◽  
Qizhi He ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lynch Syndrome ◽  
Germline Mutation

Prospective Determination of Prevalence of Lynch Syndrome in Young Women With Endometrial Cancer

2007 ◽  
Vol 25 (33) ◽  
pp. 5158-5164 ◽  
Author(s):  
Karen H. Lu ◽  
John O. Schorge ◽  
Kerry J. Rodabaugh ◽  
Molly S. Daniels ◽  
Charlotte C. Sun ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Germline Mutation ◽  
Age Of Onset ◽  
Cancer Syndrome ◽  
Degree Relative ◽  
Entire Cohort ◽  
Tumor Studies ◽  
The Mean

Purpose Age younger than 50 years at the time of colon cancer diagnosis is often used as a screening criterion for Lynch syndrome (hereditary nonpolyposis colorectal cancer syndrome). The purpose of this study was to determine the prevalence of MLH1, MSH2, and MSH6 mutations in an unselected cohort of women diagnosed with endometrial cancer at age younger than 50 years. Methods A prospective, multicenter study was performed at three institutions. After written consent was obtained, germline mutation testing by full sequencing and large deletion analysis of the MLH1, MSH2, and MSH6 genes was performed. Tumor studies included immunohistochemistry of MLH1, MSH2, and MSH6; microsatellite instability analysis; and hypermethylation of the MLH1 promoter. Results Of the 100 women, nine (9%; 95% CI, 4.2 to 16.4) carried a deleterious germline mutation: seven women with mutations in MSH2, one woman with a mutation in MLH1, and one woman with a mutation in MSH6. Two additional women had molecular studies consistent with the diagnosis of Lynch syndrome. The mean body mass index (BMI) for the entire cohort was 34.4, which is significantly higher than 29.2, the mean BMI for the mutation carriers. Predictors of finding a germline mutation included having a first-degree relative with a Lynch syndrome–associated cancer, endometrial tumor with loss of MSH2 expression, tumors with high microsatellite instability, and lower BMI. Conclusion In this prospective study of endometrial cancer patients younger than age 50 years, 9% were found to carry germline Lynch syndrome–associated mutations. In addition to young age of onset, family history, BMI, and molecular tumor studies can improve the likelihood of identifying a Lynch syndrome–associated germline mutation in MLH1, MSH2, and MSH6.

Prevalence of somatic mutl homolog 1 promoter hypermethylation in Lynch syndrome colorectal cancer

Cancer ◽  
2014 ◽  
Vol 121 (9) ◽  
pp. 1395-1404 ◽  
Author(s):  
Leticia Moreira ◽  
Jenifer Muñoz ◽  
Míriam Cuatrecasas ◽  
Isabel Quintanilla ◽  
Maria Liz Leoz ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Promoter Hypermethylation ◽  
Mutl Homolog 1

A novel Q3034R BRCA2 germline mutation identified in a fallopian tube cancer patient

2003 ◽  
Vol 191 (2) ◽  
pp. 211-214 ◽  
Author(s):  
Francesco Baudi ◽  
Loredana De Paola ◽  
Barbara Quaresima ◽  
Maria Concetta Faniello ◽  
Giuseppina Fersini ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Fallopian Tube ◽  
Germline Mutation ◽  
Fallopian Tube Cancer

scholarly journals A tumor association to be aware: endometrial cancer and colon cancer in relation to lynch syndrome

2022 ◽  
Author(s):  
Behyamet Onka ◽  
Daoud ali Mohamed ◽  
Romeo Thierry Tessi Yehouenou ◽  
Boris Adeyemi ◽  
Wend-Yam Mohammed Traore ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Molecular Biology ◽  
Lynch Syndrome ◽  
Genetic Disorder ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System ◽  
Mutl Homolog 1 ◽  
Tumor Association

lynch syndrome (LS) is an autosomal dominant genetic disorder with incomplete penetration caused by a germline mutation in one of the genes of the deoxyribonucleic acid (DNA) mismatch repair system (MMR) namely: mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MHS6), post-meiotic segregation increased 1 homolog 2 (PMS2) or the EpCAM (Epithelial CellAdhesionMolecule) gene, which causes the inactivation of MSH2. Patients with this syndrome have a high relative risk of developing cancers at a young age, led by colorectal cancer (CRC) and endometrial cancer in females. The diagnosis is suspected when the patient’s personal and family history meets the Amsterdam or Bethesda criteria. It is guided by immunohistochemistry (IHC) and/or molecular biology that show loss of expression of one or more proteins of the MMR system and microsatellite instability on tumor DNA. In case of positive IHC and/or molecular biology, the patient should be referred to an oncogenetic consultation for a definitive diagnosis. We present the case of a 49-year-old patient who presented an anaemic syndrome in metrorrhagia. After a clinical, imaging, biological and anatomopathological examination, the diagnosis of LS was made.

scholarly journals Universal screening for Lynch syndrome among patients with colorectal cancer: patient perspectives on screening and sharing results with at-risk relatives

2017 ◽  
Vol 16 (3) ◽  
pp. 377-387 ◽  
Author(s):  
Jessica Ezzell Hunter ◽  
Kathleen A. Arnold ◽  
Jennifer E. Cook ◽  
Jamilyn Zepp ◽  
Marian J. Gilmore ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
At Risk ◽  
Lynch Syndrome ◽  
Cancer Patient ◽  
Universal Screening ◽  
Colorectal Cancer Patient ◽  
Patient Perspectives

Improving detection of Lynch syndrome using a reflex immunohistochemistry algorithm for all patients with newly diagnosed colorectal cancer.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 98-98
Author(s):  
Minggui Pan ◽  
Elizabeth Hoodfar ◽  
JoAnn Bergoffen ◽  
Regan Fulton ◽  
Laura Hofmeister ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Germline Mutation ◽  
Detection Rate ◽  
Promoter Hypermethylation ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Newly Diagnosed ◽  
Mlh1 Promoter ◽  
Mmr Proteins

98 Background: Identifying patients with Lynch syndrome has profound impact on the clinical care of patients and their families. Previous guidelines based on family history alone have shown low sensitivity. In our medical center, the detection rate of Lynch syndrome was <1% among colorectal cancer cases. Methods: We have developed a system-based algorithm using centralized testing by immunohistochemistry (IHC) for four mismatched repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2) as a screening method for all newly diagnosed colorectal cancer patients, followed by step wise testing of BRAF mutation, MLH1 promoter hypermethylation, +/- microsatellite instability, and germline mutation. Results: From April 1, 2011, to July 11, 2012, we have screened 116 patients. IHC detected absent expression of at least one of the MMR proteins in 18 cases. Three cases showed missing expression of MSH2/MSH6 and the presence of a germline mutation in MSH6 was confirmed in two cases. The newest case is still being investigated for germline mutation. Of the remaining 15 cases, 10 showed the presence of BRAF V600E mutation, two showed hypermethylation of the MLH1 promoter, and one showed germline MLH1 mutation. Two cases showed no BRAF V600E mutation, no MLH1 promoter hypermethylation or germline gene mutation. Overall, of 116 cases, three cases have confirmed Lynch syndrome with the detection of a germline mutation, two cases most likely have Lynch syndrome but without any detectable germline mutation of MLH1 or PMS2 using the current detecting methods. Conclusions: Our system-based screening algorithm using reflex immunohistochemistry of four MMR proteins has resulted in excellent detection rate of approximately 4% to 5% (5 out of 116 cases), consistent with the expected Lynch syndrome prevalence rate in the population. This represents a marked improvement over our previous family history-based approach in Lynch syndrome screening.

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