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Colorectal cancer (CRC), the 3rd most frequent cancer worldwide, affects both men and women. This pathology arises from the progressive accumulation of genetic and epigenetic alterations. In this study, KRAS, NRAS, PIK3CA, and BRAF gene mutations, mismatch repair (MMR) genes methylation profile, microsatellite instability (MSI) and CpG Island Methylator Phenotype (CIMP) status were assessed. The associations of these molecular features with clinicopathological data were also investigated. A hundred and eight unselected CRC samples and their histological and clinical data, were gathered between 2017 and 2020. The prevalence of KRAS, NRAS and BRAF gene mutations was similar to that described in other populations. 28.7% of tumors were KRAS-mutated, mostly in men, distal location, with a CIMP-negative status. BRAFV600E frequency was 6.5% and associated with MSI (p = 0.048), MLH1-methylated (p 0.001) and CIMP-High (p 0.001) status. We also confirmed that BRAFV600E tumors were more prevalent in older women and proximal location. A striking different result was the lack of most common variants in the PIK3CA gene. A complete absence of PIK3CA-mutated tumors in a population has not been previously reported. Among MMR genes, the only with an aberrant methylation pattern was MLH1 gene. Its frequency was 9.25%, lower than previously reported. Methylated tumors were most frequent in patients older than 70 years old and proximal tumor location. Finally, CIMP-High status was mainly observed in moderately differentiated tumors with a rate of 15.7%. Our findings were consistent with previous reports in other populations, but also showed some features unique to our cohort. This study is the first to report the analysis of a large number molecular biomarkers of CRC in Uruguay and one of the few performed in Latin-America.

Peutz-Jeghers Syndrome (PJS) is characterized by intestinal polyposis, mucocutaneous pigmentation and an increased risk of developing multi-organ cancer, mainly in the gastrointestinal tract. Germline mutations of the STK11 gene are usually responsible for this syndrome. The aim of the present work is to report the case of a Uruguayan young patient with an atypical presentation of PJS. Extensive clinical data from the patient was obtained. Characteristic clinical diagnosis based on the presence of mucocutaneous pigmentation of the lips and oral mucosa and gastrointestinal hamartomatous polyps appeared several years later of the first gastrointestinal event (classified as “juveline polyp”) which deferred the molecular diagnosis. Complete sequencing of the STK11 gene was performed by NGS in the proband and his parents. The patient presented a novel large deletion spanning exon 5 to 10 of STK11 gene. This mutation was absent in both parents.

Familial adenomatous polyposis (FAP) is an autosomal dominant genetic condition, caused by mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. Desmoid tumors (DTs) are seen in 15% to 20% of FAP patients. Specific location of mutation serves as a guide to predict colonic and extra colonic manifestations and their aggressiveness. A severe FAP-phenotypic family was registered in a genetic counselling high-risk Uruguayan hereditary cancer clinic. Proband's DNA was analysed by NGS, detecting a pathogenic mutation in APC gene. All willing family members were counselled and encouraged to be tested. Here we report a kindred formed by 16 individuals with a very severe FAP phenotype. A two-base deletion mutation: c.4393_4394delAG in APC gene and a consequent premature stop codon was detected. DTs were diagnosed in 6 individuals, ranging from 2 to 25 years of age. The causes of death were diverse: gastric cancer, rectal cancer and desmoid tumor. The already described genotype-phenotype correlation has proved its worth in this family, as clinical features reflect the mutation location at 3' end of APC gene. The inheritable and lethal nature of the disease needs a tailored follow up approach in order to reduce mortality, optimize local tumor control, and preserve patients' quality of life.

Background In the ongoing GEnotipo, Fenotipo y Ambiente de la HiperTension Arterial en UruguaY (GEFA-HT-UY) study, we applied standardized epidemiological methods to determine complex phenotypes including blood pressure (BP). In this report, we present the quality control of the conventionally measured BP. Methods Three trained observers measured BP five times consecutively in the seated position at each of two home visits and one clinic visit according to the guidelines of the European Society of Hypertension. On 1 December 2013, 4379 single BP readings in 170 participants were available for analysis. Results Fewer BP readings than the five planned per contact occurred only at one home visit. Among observers, the frequency of identical consecutive readings for systolic or diastolic BP varied from 0 to 4.2%. The occurrence of odd readings ranged from 0.1 to 0.6%. Only 21.6% of the systolic and diastolic BP readings ended on zero (expected 20%). At home visits, there was a progressive decline in BP from the first to the fifth reading. The average of the five BP readings also decreased from the first to the second home visit (-5.63/-2.34 mmHg). Conclusions Our study highlighted the necessity to implement a stringent quality control of the conventionally measured BP. The procedures set up in the GEFA-HT-UY study are resulting in a well-defined BP phenotype, which is consistent with that in other population studies. Blood Press Monit 19: 339-345