- Verónica García
- Fátima Mercadillo
Lynch syndrome is a very complex entity associated with high risks for a wide variety of malignancies, including colorectal, endometrial, ovarian, gastric, urinary tract, pancreatic, biliary, small intestinal, prostatic, and brain cancers. Until now, the malignancies developed in people with Lynch syndrome were treated exactly in the same way as their sporadic counterparts. However, recent therapeutic advances in the immunologic effects of microsatellite instability (MSI), the hallmark of Lynch syndrome associated tumours, have resulted in important changes in the treatment of these patients.
MSI, by definition, is characterised by the somatic accumulation of mutations, which subsequently produce potentially antigenic frameshift neopeptides that account for the infiltrating lymphocyte reaction classically observed in Lynch-associated tumours. The recent emergence of immune checkpoint inhibitors that work on the patients’ own immune system has led to the use of this underlying biological characteristic to advance in the treatment of Lynch syndrome-associated tumours.
The Familial Cancer Clinical Unit (FCCU) is not only committed to screening blood samples with the aim of identifying germline mutations, but also to analysing tumour samples to determine their microsatellite status. Both findings play a critical role in the understanding of the molecular drivers of malignancy and the implementation of innovative precision-based therapies.
- (2019). POT1 and Damage Response Malfunction Trigger Acquisition of Somatic Activating Mutations in the VEGF Pathway in Cardiac Angiosarcomas. J. Am. Heart Assoc. 8, e012875. CNIO Publication.
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- (2019). Intermediate-onset colorectal cancer: A clinical and familial boundary between both early and late-onset colorectal cancer. PLoS One 14, e0216472. CNIO Publication. Open Access
- (2019). Redefining synchronous colorectal cancers based on tumor clonality. Int J Cancer 144, 1596-1608. CNIO Publication.
- (2019). Association of polyps with early-onset colorectal cancer and throughout surveillance: novel clinical and molecular implications.. Cancers 11, pii: E1900. CNIO Publication.
- (2018). Association between germline mutations in BRF1, a subunit of the RNA Polymerase III Transcription Complex, and Hereditary Colorectal Cancer. Gastroenterology 154, 181-194. CNIO Publication.
- (2018). Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis. Mol Can 17, 23. CNIO Publication. Open Access
- (2018). Novel clinical and molecular findings in Spanish patients with naevoid basal cell carcinoma syndrome. Brit J Dermatol 178, 198-206. CNIO Publication.
- (2018). Comment on ‘Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system’. Br J Cancer 118, E3. CNIO Publication.
- (2018). Germline variation in the oxidative DNA repair genes NUDT1 and OGG1 is not associated with hereditary colorectal cancer or polyposis. Hum Mutat 39, 1214-1225. CNIO Publication.
- (2018). Differential clinicopathological and molecular features within late-onset colorectal cancer according to tumor location. Oncotarget 9, 15302-15311. CNIO Publication. Open Access
- (2018). Clinical and functional characterization of the CDH1 germline variant c.1679C>G in three unrelated families with hereditary diffuse gastric cancer. Eur J Hum Genet 26, 1348-1353. CNIO Publication.
- (2018). Whole Exome Sequencing identifies PLEC, EXO5 and DNAH7 as novel susceptibility genes in testicular cancer. Int J Cancer 143, 1954-1962. CNIO Publication.
- (2017). Genetic variation in the NEIL2 DNA glycosylase gene is associated with oxidative DNA damage in BRCA2 mutation carriers. Oncotarget 8, 114626-114636. CNIO Publication. Open Access
- (2017). NOMO-1 gene is deleted in early-onset colorectal cancer. Oncotarget 8, 24429-24436. CNIO Publication.
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- (2017). Characterisation of the novel deleterious RAD51C p.Arg312Trp variant and prioritisation criteria for functional analysis of RAD51C missense changes.. Br J Cancer 117, 1048-1062. CNIO Publication.
- (2017). The wide spectrum of POT1 gene variants correlates with multiple cancer types.. Eur J Hum Genet 25, 1278-1281. CNIO Publication.
- (2017). Almost 2% of Spanish breast cancer families are associated to germline pathogenic mutations in the ATM gene.. Breast Cancer Res Treat 161, 117-134. CNIO Publication.
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- (2016). Comment on ‘Wild-type APC prediction of poor prognosis in microsatellite-stable proximal colorectal cancer differs according to the age of onset’.. Br J Cancer 114, e7. CNIO Publication.
- (2016). Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis. Sci Rep 6, 20697. CNIO Publication. Open Access
- (2016). Unsupervised Analysis of Array Comparative Genomic Hybridization Data from Early-Onset Colorectal Cancer Reveals Equivalence with Molecular Classification and Phenotypes.. Neoplasia 19, 28-34. CNIO Publication.
- (2016). Molecular insights into the OGG1 gene, a cancer risk modifier in BRCA1 and BRCA2 mutations carriers.. Oncotarget 7, 25815-25825. CNIO Publication.
- (2016). Germline missense pathogenic variants in the BRCA1 BRCT domain, p.Gly1706Glu and p.Ala1708Glu, increase cellular sensitivity to PARP inhibitor Olaparib by a dominant negative effect.. Hum Mol Genet 25, 5287-5299. CNIO Publication.
- (2015). Deletion At 6Q24.2-26 Predicts Longer Survival Of High-Grade Serous Epithelial Ovarian Cancer Patients.. Mol Oncol 9, 422-436. CNIO Publication.
- (2015). DNA copy number profiling reveals different patterns of chromosomal instability within colorectal cancer according to the age of onset.. Mol Carcinogen (in press). CNIO Publication.
- (2015). Genome-wide linkage analysis and tumoral characterization reveal heterogeneity in familial colorectal cancer type X.. J Gastroenterol 50, 657-666. CNIO Publication.
- (2015). Classifying early-onset colorectal cancer according to tumor location: new potential subcategories to explore.. Am J Cancer Res 5, 2308-2313. CNIO Publication.
- (2015). Impaired DNA repair capacity and gene expression indicate haploinsufficiency in healthy heterozygous BRCA1 mutation carriers.. Breast Cancer Res Treat 152, 271-282. CNIO Publication.
- (2015). Germline Mutations in FAN1 Cause Hereditary Colorectal Cancer by Impairing DNA Repair.. Gastroenterology 149, 563-566. CNIO Publication.
- (2015). POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance.. Genet Med 18, 325-342. CNIO Publication.
- (2015). Array CGH Analysis of Paired Blood and Tumor Samples from Patients with Sporadic Wilms Tumor.. PLoS ONE 10, e0136812. CNIO Publication.
- (2015). A mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li-Fraumeni-like families.. Nat Communications 6, 8383. CNIO Publication.
- (2015). Impact of chemotherapy on telomere length in sporadic and familial breast cancer patients.. Breast Cancer Res Treat 149, 385-394. CNIO Publication.
- (2015). Whole-Exome Sequencing Identifies MDH2 as a New Familial Paraganglioma Gene.. J Natl Cancer I 107, djv053. CNIO Publication.