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Background: Approximately 15% of colorectal cancers (CRCs) are deficient in DNA mismatch repair proteins (dMMR), a characteristic that can occur in both sporadic and hereditary CRC. Due to sparse studies on dMMR CRC in the Brazilian population, we conducted a retrospective analysis of referral rates for Genetic Cancer Risk Assessment of this population and also describing clinical and molecular characterization of these tumors., Methods: A retrospective, longitudinal, and unicenter study that included patients with dMMR CRC detected by IHC analysis from Pathology Database of our institution, from January 2015 to July 2017., Results: MMR IHC testing was performed in 998 CRC tumors, and 78 tumors (7.8%) had dMMR. The mean age at diagnosis was 56.8 years (17-90), and most patients were female (41 out of 78, 52.6%). Of the 52 patients with right-sided CRC, 40 tumors (77%) had loss of the MLH1 and/or PMS2 expression, and 12 tumors (23%) had loss of MSH2 and/or MSH6 expression (p = 0.005). From 78 patients with dMMR CRC, only 43 patients (55.1%) were referred for genetic counseling (GC), and of them, only 33 patients (76.7%) really went to GC consultation. A total of 21 patients with dMMR CRC performed genetic testing., Conclusion: Overall, genetic referral was less than expected in our population. Most of dMMR CRC patients did not receive GC, even in a cancer center, either due to the absence of referral or personal decision and few patients who pursued genetic counseling performed genetic testing., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To report the frequency of Lynch syndrome (LS) in a cohort of patients from Southeast Brazil bearing endometrial cancer (EC), using a tumor screening universal approach., Methods: A total of 242 endometrial carcinomas were screened by immunohistochemistry (IHC) and microsatellite instability (MSI) for detection of DNA mismatch repair deficiency (dMMR). MLH1 methylation was assessed to identify sporadic cases. Patients with dMMR tumors were recruited for germline variant analysis by next-generation sequencing of the MLH1, MSH2, MSH6, PMS2, and EPCAM genes., Results: Ninety-three out of 242 tumors (38.5%) were classified as dMMR based on MSI and IHC results. Of these, 54 cases were selected for germline analysis, and 37/54 (68.5%) were available for sequencing. Ten patients (10/37, 27%) harbored germline pathogenic or likely pathogenic variants, most of them in the MSH6 gene (4/10, 40%). Seven variants of uncertain significance were found. Eight novel germline variants were identified. The LS prevalence in our cohort was of at least 4.1%. LS patients presented lower mean age at cancer diagnosis compared with patients diagnosed with sporadic EC. Individuals with dMMR tumors, without germline pathogenic variants detected in LS-genes ("Lynch-like" syndrome), had an intermediate mean age at cancer diagnosis between LS and sporadic cases., Conclusion: This is the first report of the LS prevalence in EC screened by a universal approach in Brazil. Our findings contribute to a better understanding of the mutational landscape of this syndrome in Brazil, which is relevant for improved identification, genetic counseling, prevention and control of cancer in LS., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest regarding the research, authorship, and/or publication of this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: This study is part of Brazil's Craniofacial Project, which is the first initiative for a national characterization of craniofacial healthcare in Brazil. Our main aim was to describe the status of clinical genetics in the Brazilian Reference Network for Craniofacial Treatment., Design: All services (n = 29) listed in the Brazilian Reference Network for Craniofacial Treatment until October 2003 were contacted and invited to complete a questionnaire. Information regarding the general characteristics of the services, availability of genetic services, and genetic service providers was collected., Results: The response rate was 86.2% (n = 25). Thirteen responding teams had clinical geneticists. Teams were predominantly located in the southeast region and affiliated with universities. Family interest in genetic counseling was reported by 95.7% (22/23) of the services. Although 80% of the responding services reported offering genetic counseling, only 45% (9/20) provided genetic counseling guided by clinical geneticists., Conclusion: Availability and access to genetic evaluation and counseling are still rudimentary in Brazil. Many services report family interest in genetic counseling, but there are few teams with clinical geneticists. Inclusion of this specialist on craniofacial teams is crucial to patient care. Development of standard guidelines for genetic evaluation of selected craniofacial anomalies and for local genetic counseling (e.g., for nonsyndromic cleft lip or palate) could be an alternative for improving current deficiencies in the system. Strengthening the degree of coordination and communication among craniofacial teams represents another important goal.