Loss-of-function germline variants of MLH1 cause Lynch syndrome. Here, we present the case of a 43-year-old male patient diagnosed with cecal and transverse colon adenocarcinomas. The characteristics of the case met the revised Bethesda guidelines, and the tumors demonstrated a high frequency of microsatellite instability. Genetic testing for mismatch repair genes (indicative of Lynch syndrome) revealed a novel heterozygous germline pathogenic variant, NM_000249.4:c.856A>T/NP_000240.1:p.(Lys286Ter), in MLH1.
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http://dx.doi.org/10.1038/s41439-024-00294-9 | DOI Listing |
Zhonghua Wei Chang Wai Ke Za Zhi
December 2024
Fam Cancer
December 2024
Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
Lynch syndrome (LS) is an autosomal dominant hereditary cancer predisposition syndrome whereby the lifetime risk of developing gastrointestinal and genitourinary cancers rises by to over 50%. It is caused by heterozygous variants in the DNA mismatch repair genes- MLH1, MSH2, MSH6 and PMS2, with the majority detected in MLH1 and MSH2. Recurrently observed LS-associated variants in apparently unrelated individuals have either arisen de novo in different families due to mutation hotspots or are inherited from a common ancestor (founder) that lived several generations back.
View Article and Find Full Text PDFLancet Oncol
December 2024
Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address:
Background: Gliomas are a major cause of cancer-related death among children, adolescents, and young adults (age 0-40 years). Primary mismatch repair deficiency (MMRD) is a pan-cancer mechanism with unique biology and therapeutic opportunities. We aimed to determine the extent and impact of primary MMRD in gliomas among children, adolescents, and young adults.
View Article and Find Full Text PDFCancer Rep (Hoboken)
December 2024
Department of Pathology, The University of Chicago, Chicago, Illinois, USA.
Background: Rapid and accurate identification of mismatch repair (MMR) deficiency and Lynch syndrome is critical in the prognostication and clinical management of patients with colorectal carcinoma.
Case Description: We describe here a young woman who developed a locally aggressive rectal adenocarcinoma with intact MMR protein expression by immunohistochemistry and absence of histologic evidence of MMR deficiency-associated increased tumoral immune response. Germline DNA-targeted sequencing identified MSH2 variant p.
J Natl Compr Canc Netw
December 2024
National Comprehensive Cancer Network.
Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing.
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