Pitfalls in the diagnosis of biallelic PMS2 mutations

Abstract Constitutional Mismatch Repair Deficiency (CMMR-D) syndrome is an inherited childhood cancer syndrome due to bi-allelic mutations in one of the four DNA mismatch repair genes involved in Lynch syndrome. The tumor spectrum of this syndrome includes hematological, brain and Lynch syndrome associated malignancies, with an increased risk of synchronous and metachronous cancers, and signs of Neurofibromatosis type-1 syndrome such as café-au-lait macules during the first three decades of life. Here, we report the first Argentinian patient with CMMR-D syndrome, focusing on her history of cancer and gastrointestinal manifestations, and the challenging molecular algorithm to finally reach her diagnosis.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research

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Authors: Abdel-Rahman O Abstract Objectives: The current study aims to evaluate the correlation between pre-diagnostic body mass index (BMI) as well as BMI trajectory in relation to lung cancer development and mortality risks. Methods: This analysis is based on Prostate, Lung, Colorectal, and Ovary (PLCO) trial datasets. Based on 145544 participants with complete information about pre-diagnostic BMI/BMI trajectory, associations of BMI measurements during adult life (at 20 years, 50 years and at enrolment into the study) with lung cancer development and mortality risks were determined. Multivariate Cox regression mo...
Source: Expert Review of Respiratory Medicine - Category: Respiratory Medicine Tags: Expert Rev Respir Med Source Type: research
Authors: Cheung PK, Ma MH, Tse HF, Yeung KF, Tsang HF, Chu MKM, Kan CM, Cho WCS, Ng LBW, Chan LWC, Wong SCC Abstract Introduction: Metabolomics, the study of metabolites, is a promising research field for cancers. The metabolic pathway in a tumor cell is different from a normal tissue cell. There are two approaches to study the metabolism, targeted and untargeted. The general approach is that metabolomic data are interpreted by bioinformatics tools correlating with metabolomic databases to obtain significant findings. With the use of specific analysis tools, such as nuclear magnetic resonance (NMR) and mass spectro...
Source: Expert Review of Molecular Diagnostics - Category: Laboratory Medicine Tags: Expert Rev Mol Diagn Source Type: research
Publication date: Available online 15 August 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): Hudson W. Coates, Ngee Kiat Chua, Andrew J. BrownAbstractCholesterol accumulation is a hallmark of prostate cancer (PCa) enabled by upregulation of its synthesis, which presents a potential therapeutic target. This pathway is suppressed by the E3 ubiquitin ligase membrane-associated RING-CH-type finger 6 (MARCH6); however, little is known of MARCH6 regulation, particularly at the transcriptional level. Here, we consulted large transcriptomic PCa datasets to investigate transcription ...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research
November 23-24, 2019
Source: The Journal of Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Tags: Announcement Source Type: research
Correction: PARP-1 inhibitor modulate β-catenin signaling to enhance cisplatin sensitivity in cancer cervix. Oncotarget. 2019 Jul 30;10(46):4802 Authors: Mann M, Kumar S, Chauhan SS, Bhatla N, Kumar S, Bakhshi S, Gupta R, Sharma A, Kumar L Abstract [This corrects the article DOI: 10.18632/oncotarget.27008.]. PMID: 31413820 [PubMed - in process]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Authors: Hamdan D, Nguyen TT, Leboeuf C, Meles S, Janin A, Bousquet G Abstract Breast cancer remains a major health issue in the world with 1.7 million new cases in 2012 worldwide. It is the second cause of death from cancer in western countries. Genomics have started to modify the treatment of breast cancer, and the developments should become more and more significant, especially in the present era of treatment personalization and with the implementation of new technologies. With molecular signatures, genomics enabled a de-escalation of chemotherapy and personalized treatments of localized forms of estrogen-depend...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
The objective of this study was to determine whether osteoarthritis had an impact on outcomes of prostate cancer including death, local recurrence and/or metastasis and to determine whether cartilage oligomeric matrix protein was involved. We performed a retrospective case-control study of patients with prostate cancer with and without the diagnosis of osteoarthritis and completed immunohistochemistry (IHC) analysis of prostate (n=20) and lymph node (n=7) surgical specimens. We evaluated death, local recurrence and metastatic disease by various IHC biomarkers including prostate specific membrane antigen (PSMA), cartilage o...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Abstract Inherited mono-allelic mutation in one of the 4 major MMR genes results in Lynch syndrome which predisposes, in adulthood, mainly to colorectal and endometrial tumors characterized by microsatellite instability (MSI phenotype). Individuals with bi-allelic mutations of one of these genes developed early and multiple malignancies, most often in childhood. This recessively inherited condition is named CMMRD for Constitutional Mismatch Repair Deficiency. The spectrum of tumors is distinct from Lynch syndrome. Malignant brain tumors are at least as frequent as gastrointestinal tumors and in more than a third o...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research
Abstract Constitutional mismatch repair deficiency (CMMRD) syndrome is one of the rare diseases associated with a high risk of cancer. Causative mutations are found in DNA mismatch repair genes PMS2, MSH6, MSH2 or MLH1 that are well known in the context of Lynch syndrome. CMMRD follows an autosomal recessive inheritance trait and is characterized by childhood brain tumors and hematological malignancies as well as gastrointestinal cancer in the second and third decades of life. There is a high risk of multiple cancers, occurring synchronously and metachronously. In general, the prognosis is poor. About one third of...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
ConclusionsCMMRD is rare, but, especially in areas where founder mutations for LS and consanguinity are common, pediatricians should be aware of it since they are the first to encounter these children. Early diagnosis will enable tailored cancer surveillance in the entire family and a discussion regarding prenatal genetic diagnosis.
Source: Pediatric Blood and Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
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