Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections.

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

Colorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America.The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations.The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P = 0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3–T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P = 0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P = 0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P = 0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P = 0.005) and report a family history of cancer (17.4% vs 10.2%; P = 0.001).To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations.

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