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Int J Clin Oncol 2021 Jun 11. Epub 2021 Jun 11.

Division of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center, Saitama, 362-0806, Japan.

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients. Read More

Orphanet J Rare Dis 2021 Jun 8;16(1):261. Epub 2021 Jun 8.

Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Rd., Beijing, 100038, China.

Objective: To report Peutz-Jeghers syndrome (PJS) cases with non-definitive clues in the family or personal history and finally diagnosed through pathological examination and STK11 gene mutation test.

Clinical Presentation And Intervention: PJS was suspected in 3 families with tortuous medical courses. Two of them had relatives departed due to polyposis or colon cancer without pathological results, and the other one had been diagnosed as hyperplastic polyposis before. Read More

Cureus 2021 May 2;13(5):e14804. Epub 2021 May 2.

Department of Neurosurgery, University of Texas Medical Branch, Galveston, USA.

Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal-dominant genetic disorder of DNA mismatch repair associated with many forms of cancer, especially colorectal and including renal cell. In this report, we present a case of a patient with a known history of HNPCC whose first presentation of renal cell carcinoma (RCC) was associated with a symptomatic intracranial lesion. After intracranial imaging, resection, and pathologic examination, the lesion was revealed to be of RCC origin. Read More

MMW Fortschr Med 2021 06;163(11):41-44

- FÄ für Humangenetik -, Med.-Genetisches Zentrum \/MGZ, Bayerstraße 3 - 5, 80335, München, Deutschland.

Rev Med Liege 2021 May;76(5-6):327-336

Service de Génétique Humaine, CHU Liège et GIGA, ULiège; ERN GETURIS, Belgique.

A personal or family history of cancer has now become the primary cause of genetic consultations. In recent years, various genes have been identified that are associated with a more or less marked genetic predisposition to the development of cancers. The syndrome associated with the hereditary risk of breast and ovarian cancer and the Lynch syndrome are the most frequent ones, but there are many other, much less common, situations associated with familial cancer risk. Read More

Clin Exp Gastroenterol 2021 24;14:181-197. Epub 2021 May 24.

Department of Gastroenterology, Aalborg Hospital, Aalborg, Denmark.

During the recent years, immune checkpoint-based therapy has proven highly effective in microsatellite instable (MSI) solid tumors irrespective of organ site. MSI tumors are associated with a defective mismatch repair (MMR) system and a highly immune-infiltrative tumor microenvironment-both characteristics of Lynch syndrome. Lynch syndrome is a multi-tumor syndrome that not only confers a high risk of colorectal and endometrial cancer but also cancer in, eg the upper urinary tract, ovaries, and small bowel. Read More

Cancers (Basel) 2021 May 26;13(11). Epub 2021 May 26.

Discipline of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL A1B 3V6, Canada.

Hereditary diffuse gastric cancer (HDGC) is a rare signet-ring cell adenocarcinoma (SRCC) linked to (E-cadherin) inactivating germline mutations, and increasingly other gene mutations. Female mutation carriers have additional risk of lobular breast cancer. Risk management includes prophylactic total gastrectomy (PTG). Read More

Cancers (Basel) 2021 May 13;13(10). Epub 2021 May 13.

Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.

Lynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are hereditary disorders characterised by a highly increased risk of cancer development. This is due to germline aberrations in the mismatch repair (MMR) genes, which results in a high mutational load in tumours of these patients, including insertions and deletions in genes bearing microsatellites. This generates microsatellite instability and cause reading frameshifts in coding regions that could lead to the generation of neoantigens and opens up avenues for neoantigen targeting immune therapies prophylactically and therapeutically. Read More

Int J Mol Sci 2021 May 11;22(10). Epub 2021 May 11.

Research Unit, University Hospital Son Espases, 07120 Palma, Spain.

Even though colorectal cancer (CRC) is one of the most preventable cancers, it is currently one of the deadliest. Worryingly, incidence in people <50 years has increased unexpectedly, and for unknown causes, despite the successful implementation of screening programs in the population aged >50 years. Thus, there is a need to improve early diagnosis detection strategies by identifying more precise biomarkers. Read More

Sci Rep 2021 May 31;11(1):11401. Epub 2021 May 31.

Research Unit, Ålesund Hospital, Møre and Romsdal Hospital Trust, Ålesund, Norway.

Individuals with Lynch syndrome (LS), have an increased risk of developing cancer. Common genetic variants of telomerase reverse transcriptase (TERT) have been associated with a wide range of cancers, including colorectal cancer (CRC) in LS. We combined genotype data from 1881 LS patients, carrying pathogenic variants in MLH1, MSH2 or MSH6, for rs2075786 (G>A, intronic variant), 1207 LS patients for rs2736108 (C>T, upstream variant) and 1201 LS patients for rs7705526 (C>A, intronic variant). Read More

Sci Rep 2021 May 31;11(1):11385. Epub 2021 May 31.

Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.

The G84E germline mutation of HOXB13 predisposes to prostate cancer and is clinically tested for familial cancer care. We investigated the HOXB locus to define a potentially broader contribution to prostate cancer heritability. We sought HOXB locus germline variants altering prostate cancer risk in three European-ancestry case-control study populations (combined 7812 cases and 5047 controls): the International Consortium for Prostate Cancer Genetics Study; the Nashville Familial Prostate Cancer Study; and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Read More

Asian Pac J Cancer Prev 2021 May 1;22(5):1477-1483. Epub 2021 May 1.

Division of Medical Genetics, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.

Background: Lynch syndrome increases lifetime risk of endometrial cancer to 40-60%. Screening with molecular tumor testing for mismatch repair (MMR) proteins have been recommended. This study aims to evaluate the incidence of MMR deficiency and germline mutation in endometrial cancer Thai patients. Read More

Sci Rep 2021 May 27;11(1):11135. Epub 2021 May 27.

Fundación Publica Galega de Medicina Xenómica, SERGAS, Grupo de Medicina Xenómica-USC, Instituto de Investigación Sanitaria de Santiago (IDIS), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain.

Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Read More

Crit Rev Oncol Hematol 2021 May 25;163:103338. Epub 2021 May 25.

Department of Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands. Electronic address:

Lynch syndrome (LS) is a hereditary cancer syndrome that accounts for 3% of all new colorectal cancer (CRC) cases. Patients carry a germline pathogenic variant in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6 or PMS2), which encode proteins involved in a post-replicative proofreading and editing mechanism. The clinical presentation of LS is highly heterogeneous, showing high variability in age at onset and penetrance of cancer, which may be partly attributable to the molecular profiles of carcinomas. Read More

Br J Surg 2021 May;108(5):484-498

Centre for Hereditary Tumours, Bethesda Hospital, Duisburg, Germany.

Background: Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged. Read More

BMC Cancer 2021 May 26;21(1):617. Epub 2021 May 26.

Department of Cancer Genetics, St. James' Hospital, James' Street, Dublin, Ireland.

Background: Lynch syndrome (LS) is an autosomal dominant hereditary cancer syndrome responsible for 2-4% of hereditary colorectal cancers (CRC). Mismatch repair protein deficiency (dMMR) is a characteristic feature of LS. It has been associated with a poor response to standard chemotherapy in metastatic colorectal cancer (mCRC). Read More

Cureus 2021 Apr 20;13(4):e14582. Epub 2021 Apr 20.

Hematology/Oncology, Henry Ford Health System, Jackson, USA.

Muir-Torre syndrome (MTS) is an autosomal dominant condition characterized by dermatological tumors along with visceral malignancies. The dermatological manifestations include recurrent sebaceous adenomas and keratoacanthomas. The commonly seen visceral malignancies are colorectal, gynecological, and urological. Read More

PLoS One 2021 19;16(5):e0250379. Epub 2021 May 19.

Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.

Background: Integration of genetic testing into routine oncology care could improve access to testing. This systematic review investigated interventions and the tailored implementation strategies aimed at increasing access to genetic counselling and testing and identifying hereditary cancer in oncology.

Methods: The search strategy results were reported using the PRISMA statement and four electronic databases were searched. Read More

Cancer Res 2021 May 18;81(10):2760-2773. Epub 2021 Mar 18.

Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Lynch syndrome is the most common cause of hereditary colorectal cancer and is secondary to germline alterations in one of four DNA mismatch repair (MMR) genes. Here we aimed to provide novel insights into the initiation of MMR-deficient (MMRd) colorectal carcinogenesis by characterizing the expression profile of MMRd intestinal stem cells (ISC). A tissue-specific MMRd mouse model (Villin-Cre;Msh2 ) was crossed with a reporter mouse () to trace and isolate ISCs (Lgr5+) using flow cytometry. Read More

Clin Transl Gastroenterol 2021 May 17;12(5):e00353. Epub 2021 May 17.

Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.

Introduction: Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer (CRC) syndrome characterized by accelerated adenoma development due to inherited (or de novo) mutations in the APC regulator of WNT signaling pathway (APC) gene. The mechanism underlying this accelerated polyp development in subjects with FAP has not been defined. Given that LGR5+ stem cells drive crypt cell proliferation, we hypothesized that FAP crypts would demonstrate aberrant leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) staining patterns. Read More

Curr Drug Targets 2021 Mar 24. Epub 2021 Mar 24.

Head and Neck Surgery, National Institute of Oncology, Budapest, Hungary.

The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. Read More

Dis Colon Rectum 2021 Apr 29. Epub 2021 Apr 29.

Cleveland Clinic, Cleveland, Ohio.

Background: Rectal cuff and anal transitional zone neoplasia is an increasing challenge in patients with familial adenomatous polyposis who have undergone restorative proctocolectomy. Its real incidence, range of severity, and treatment efficacy are poorly documented.

Objective: We sought to document the evolution of rectal cuff and anal transitional zone neoplasia and describe its management. Read More

J Hum Genet 2021 May 6. Epub 2021 May 6.

Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.

Lynch syndrome is a hereditary disease characterized by an increased risk of colorectal and other cancers. Germline variants in the mismatch repair (MMR) genes are responsible for this disease. Previously, we screened the MMR genes in colorectal cancer patients who fulfilled modified Amsterdam II criteria, and multiplex ligation-dependent probe amplification (MPLA) identified 11 structural variants (SVs) of MLH1 and MSH2 in 17 patients. Read More

Can J Gastroenterol Hepatol 2021 12;2021:6610434. Epub 2021 Apr 12.

Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.

A large number of colorectal cancers have a genetic background in China. However, due to insufficient awareness, the diagnostic rate remains low and merely 5-6% of colorectal cancer patients are diagnosed with hereditary colorectal cancer. Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease caused by mutations in the adenomatous polyposis coli (APC) gene. Read More

PLoS One 2021 4;16(5):e0250072. Epub 2021 May 4.

Division of Lower GI Surgery, Department of Surgery, Hyogo College of Medicine, Hyogo, Japan.

Circulating microRNAs (miRNAs) are considered promising biomarkers for diagnosis, prognosis, and treatment efficacy of diseases. However, usefulness of circulating miRNAs as biomarkers for hereditary gastrointestinal diseases have not been confirmed yet. We explored circulating miRNAs specific for patients with familial adenomatous polyposis (FAP) as a representative hereditary gastrointestinal disease. Read More

JAAD Case Rep 2021 May 23;11:72-73. Epub 2021 Mar 23.

Division of Dermatology, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Front Oncol 2021 16;11:652696. Epub 2021 Apr 16.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

We present an extremely rare clinical case of a 38-year-old Russian patient with multiple malignant neoplasms of the uterus and colon caused by genetically confirmed two hereditary diseases: Diamond-Blackfan anemia and Lynch syndrome. Molecular genetic research carried out by various methods (NGS, Sanger sequencing, aCGH, and MLPA) revealed a pathogenic nonsense variant in the gene: NM_000179.2: c. Read More

JNCI Cancer Spectr 2021 Apr 8;5(2):pkab022. Epub 2021 Mar 8.

Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Victoria, Australia.

It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes-people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 , 314 , 126 , 71 , and 22 ) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided >. Read More

Int J Mol Sci 2021 Apr 28;22(9). Epub 2021 Apr 28.

Department of Pathology, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain.

Biallelic germline mismatch repair (MMR) gene and mutations are an extremely rare event that causes constitutional mismatch repair deficiency (CMMRD) syndrome. CMMRD is underdiagnosed and often debuts with pediatric malignant brain tumors. A high degree of clinical awareness of the CMMRD phenotype is needed to identify new cases. Read More

Cancers (Basel) 2021 Apr 13;13(8). Epub 2021 Apr 13.

Gerontology Research Centre and Faculty of Sport and Health Sciences, University of Jyväskylä, P.O. Box 35 (VIV), 40014 Jyväskylä, Finland.

Lynch syndrome (LS) increases cancer risk. There is considerable individual variation in LS cancer occurrence, which may be moderated by lifestyle factors, such as body weight and physical activity (PA). The potential associations of lifestyle and cancer risk in LS are understudied. Read More