Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma

We report a family with an autosomal dominant inheritance of PPAP due to a c.1089C>A; p.Asn363Lys mutation in the proofreading exonuclease domain ofPOLE. Ten patients presenting a history of colorectal tumours and three patients with polyposis are indexed in this family. Three carriers (including siblings and a distant cousin at 30, 45 and 52 respectively) and another member (at 37 not tested) presented glioblastoma. This is the second family reported to carry this mutation. Among the four glioblastomas in the family that we report, both show similar pathology: giant cell glioblastoma. These cases suggest that the c.1089C>A germlinePOLE mutation may confer an increased risk of brain cancer [incidence 17.4% (4/23) in mutation carriers combining the two families]. More observations are needed to support this hypothesis. It seems that not all mutations ofPOLE are equally associated with extra-gastrointestinal tumours. Although carriers of a mutation responsible for PPAP should benefit from screening for colorectal and uterine cancer, due to the rapid evolution of glioblastoma the value of neurological follow-up and brain imaging screening remains questionable. Nevertheless, considering the limitations of standard therapy for glioblastoma, mutation status could be useful for targeting therapy. The biological mechanism linkingPOLE mutation to glioblastoma remains to be determined.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research

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In this study, we reviewed major human studies on the health risks of radiation exposure and showed that sex-related factors may potentially influence the long-term response to radiation exposure. Available data suggest that long-term radiosensitivity in women is higher than that in men who receive a comparable dose of radiation. The report on the biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences, United States emphasized that women may be at significantly greater risk of suffering and dying from radiation-induced cancer than men exposed to the same dose of radiation....
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions and Perspectives It is interesting that watershed events, such as the loss of Neu5Gc from the glycocalyx of human cells have occurred numerous times in many mammalian and other vertebrate species. These cases of convergent evolution represent precious opportunities for increased understanding of evolutionary processes. In some respects, Neu5Gc is an ideal self-molecule as it is “private” to vertebrates and, based on current data, has yet to be successfully mimicked by microbes. Against the background of this benefit, the loss of Neu5Gc appears paradoxical and may implicate strong selective regimes,...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions and Perspectives In this review, we have discussed important milestones from the early description of “Serum-sickness” as being due to antibodies directed against Neu5Gc epitopes all the way to the present-day therapeutic implications of these antibodies in cancer therapy. Some of these milestones have been represented in a concise timeline (Figure 6). While the “Xenosialitis” hypothesis is well-supported in the human-like mouse models, it has yet to be conclusively proven in humans. It remains to be seen if “Xenosialitis” plays a role in other uniquely-human diseases. FI...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion In conclusion, genes that display a correlation between DNA methylation and their expression in specific tissues are responsible for significant changes in not only in developmental stages but also in adult tissues. We made this finding by using tissues that are not in developmental stages, but have developed in adults. This can either represent a change that occurs at the developmental stage, or it can be the result of epigenetic changes. This study presents a methodology that can be used by other researchers using omics data combined with different types of NGS data, and provides them with the opportunity to ...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
We report a case of a 60-year-old female, suffering from non-small cell lung cancer (NSCLC), with refractory lower back pain, as expression of malignant psoas syndrome (MPS). MPS is a rare and difficult-to-treat cancer-pain syndrome, unresponsive to majority of analgesic therapy, related to psoas muscle metastasis; it is usually caused by different tumors such as uterus, ovary, bladder, prostate, colon-rectum, lymphoma, melanoma and sarcoma and represents an uncommon finding in NSCLC patients. PMID: 30968671 [PubMed - in process]
Source: Monaldi Archives for Chest Disease - Category: Respiratory Medicine Tags: Monaldi Arch Chest Dis Source Type: research
Di Che1†, Yanfang Yang2†, Yufen Xu1†, Zhenzhen Fang3, Lei Pi1, LanYan Fu1, Huazhong Zhou1, Yaqian Tan1, Zhaoliang Lu1, Li Li4, Qihua Liang5, Qingshan Xuan4* and Xiaoqiong Gu1,5,6* 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China 2Department of Prenatal Diagnosis, Maoming People’s Hospital, Maoming, China 3Program of Molecular Medicine, Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China 4...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Authors: Duraturo F, Liccardo R, De Rosa M, Izzo P Abstract Lynch syndrome (LS) is an autosomal dominant genetic disorder associated with germline mutations in DNA mismatch repair (MMR) genes. The carriers of pathogenic mutations in these genes have an increased risk of developing a colorectal cancer and/or LS-associated cancer. The LS-associated cancer types include carcinomas of the endometrium, small intestine, stomach, pancreas and biliary tract, ovary, brain, upper urinary tract and skin. The criteria for the clinical diagnosis of LS and the procedures of the genetic testing for identification of pathogenetic ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
(CBS Local) — The nation’s cancer death rate dropped a whopping 27 percent during the last quarter century, according to a new report by the American Cancer Society. That translates to about 2.6 million fewer cancer deaths than would have been expected if rates stayed at their peak, which was seen in 1991. “The decline in deaths is largely driven by reductions in smoking and improved treatment, as well as earlier detection for some cancers,” said lead researcher Rebecca Siegel, scientific director of surveillance research at the cancer society. The drop was driven by huge strides made in treating mo...
Source: WBZ-TV - Breaking News, Weather and Sports for Boston, Worcester and New Hampshire - Category: Consumer Health News Authors: Tags: Health News American Cancer Society Local TV talkers Source Type: news
Abstract BACKGROUND: DNA methylation is involved in numerous biologic events and associates with transcriptional gene silencing, playing an important role in the pathogenesis of endometrial cancer. ESR1/PGR frequently undergoes de novo methylation and loss expression in a wide variety of tumors, including breast, colon, lung, and brain tumors. However, the mechanisms underlying estrogen and progesterone receptors (ER/PR) loss in endometrial cancer have not been studied extensively. The aims of this study were to determine the expression of DNA (cytosine-5)-methyltransferase 3A/3B (DNMT3A/3B) in endometrial cancer ...
Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research
AbstractLynch syndrome (LS) is an autosomal-dominant inherited disorder characterized by a predisposition to colorectal cancer and extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, hepatobiliary tract, pancreas, urothelial tract, brain, and skin). Muir –Torre syndrome (MTS) is considered a phenotypical variant of LS, where patients develop sebaceous neoplasms and keratoacanthomas. Currently, only few studies and case reports suggest an association between LS and other skin cancers, such as Bowens’ disease, melanoma and squamous cell carcinoma (SCC). In this case-report we describe the...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
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