ABSTRACT
Latin-America (LATAM) is the second region in gastric cancer incidence; gastric adenocarcinoma (GA) represents 95% of all cases. We provide a mutational landscape of GA highlighting a) germline pathogenic variants associated with hereditary GA, b) germline risk variants associated with sporadic GA, and c) somatic variants present in sporadic GA in LATAM, and analyze how this landscape can be applied for precision medicine. We found that Brazil, Chile, Colombia, Mexico, Peru, and Venezuela are the countries with more published studies from LATAM explicitly related to GA. Our analysis displayed that different germline pathogenic variants for the CDH1 gene have been identified for hereditary GA in Brazilian, Chilean, Colombian, and Mexican populations. An increased risk of developing somatic GA is associated with the following germline risk variants: IL-4, IL-8, TNF-α, PTGS2, NFKB1, RAF1, KRAS and MAPK1 in Brazilian; IL-10 in Chilean; IL-10 in Colombian; EGFR and ERRB2 in Mexican, TCF7L2 and Chr8q24 in Venezuelan population. The path from mutational landscape to precision medicine requires four development levels: 1) Data compilation, 2) Data analysis and integration, 3) Development and approval of clinical approaches, and 4) Population benefits. Generating local genomic information is the initial padlock to overcome to generate and apply precision medicine.
ABSTRACT
BACKGROUND: Kaposi sarcoma may be the initial manifestation of immunodeficiency acquired syndrome (AIDS )in 30% of patients. The digestive tract is the thirth most affected site after the skin and lymph nodes. OBJECTIVE: To correlate the clinic and endoscopic manifestations of patients with AIDS. METHOD: 12 consecutive cases with AIDS and Kaposi sarcoma. We analyzed clinical data, positivity , immune state (leucocytes, lymphocytes, viral load, CD4 and CD8 counts, CD4/CD8 relation), opportunistic infections, tumors, endoscopic characteristics of the associated tumors, and histologic results. RESULTS: 12 patients. 11 men and 1 woman with an average age of 37.3 years old, a Karnofsky score X = 80%, weight X = 55.7 kg. All of them acquired the disease by sexual contact. The symptoms were weight loss in 6 cases, anemia in 6, abdominal pain 6, fever 6, melena 4, odynophagia 3, diarrhea 4, hematemesis 2, abdominal distention 2, dysphagia 2, bright red blood per rectum 1. The distribution of Kaposi sarcoma was as follows: hard palate 7, soft palate 2, larynx 3, esophagus 2, stomach 10, duodenum 2, colon 5 and anal conduct 1. The endoscopic appearance was in the majority a purple or blue elevated plaque that had various sizes. The biopsy was positive to Kaposi sarcoma in at least one lesion of each patient. The haemoglobin was x = 11.5, leukocytes X = 5463, total lymphocytes X = 2377 (35.7%), CD4 X = 247.8 (10.8%), CD8 X = 1008.7 (54.6%). CD4/CD8 relation = 0.20, T4/T8 = 0.25M, the viral load was X = 140,629 copies. CONCLUSIONS: The Kaposi sarcoma appears as a multiple lesion with diverse aspect and colors that go from purple to blue or red. There is correlation between a high number of Kaposi sarcoma lesions, affected organs, immunologic status and mortality.
