Inherited mutations in the RET proto-oncogene, which encodes a receptor tyrosine kinase, predispose individuals to the multiple endocrine neoplasia type 2 (MEN 2) cancer syndromes. The major component tumor of these syndromes is medullary thyroid carcinoma (MTC). To date, somatic mutations in RET have been identified in tumors from individuals with MEN 2 finding. RET M918T mutation is present in 95% of the MEN2B cases, and approximately 50% of sporadic MTCs harbor this mutation. We performed a mutational analysis in 17 cases of Medullary thyroid carcinoma, the somatic missense mutation at codon 918 of RET was found in 2 of the 17 MTCs, and one case presented MEN2 phenotype including MTC. The percentage of RET M918T mutation is similar in Mexican MTC patients to other series, although other mutations could be implicated in our population.

Background: Fluoropyrimidines (5-fluorouracil (5-FU), capecitabine and tegafur) are the mainstay chemotherapeutic drugs for gastrointestinal cancer. Patients with deficiency of dihydropyrimidine dehydrogenase enzyme (DPD), which interfere with the pyrimidine metabolism, could be at risk toxicity (mild, severe or lethal) because >80% of the administered 5-FU is catabolized by DPD. Previously, our group studied DPYD single-nucleotide polymorphism (SNPs) by real-time PCR assay, in 72 Mexicans. We found that frequency of SNP 85T>C and 85T>T was similar as Oriental race (2-3%), but contrast with Caucasians (0.19%), meanwhile, for SNP 496A>G which Caucasian prevalence was reported 0.8%, in our Mexican sample was very high (14%). Even though, none of our patients with toxicity grade 3-4, were positive to the SNP associated to higher toxicity (IVS14 + 1G>A). Because of this heterogeneity, we decide to sequence the complete gen in our population. Methods: We included prospectively, 19 patients of the GI Oncology Department of the National Cancer Institute of Mexico, who were treated with fluoropyrimidines. We follow them during the whole treatment. DNA was extracted from whole blood using the DNeasy blood and tissue kit (Qiagen Ltd, Crawley, UK). We use the AmpliSeq™ Designer for the full coverage of all 23 exons of DPYD gene; 25 μg of DNA was used for library construction (Ion Ampliseq Library kit 2.0), we follow the manufacturer's instructions for the target sequencing of DPYD gene with the Ion Torrent PGM platform. The data management was performed with the Ion Reporter Software of Thermo Fisher. Results: We found that 89.5% of the patients had SNPs (c.85C>T), 44.1% (c.1627A>G) and 5.2% (c.496A>G). Mean while SNPs: c.1896T>C, c.451A>G, c.771C>T, c.2384G>A, c.2605G>A, c.1462A>G, c.1422_1422delA were present in a lower frequencies. These results were associated to clinical toxicity (mucositis, neurotoxicity, hand foot syndrome, hematological toxicity and diarrhea grade >2) but there wasn't any association (chi2 test). Not a single patient were positive for IVS14 + 1G>A. Conclusion: These are the first results using NGS for DPYD gene in Mexican people. We confirm that our population had a different molecular profile that Caucasians. We need to improve the sample size, to see if we could find an association between SNPs and clinical toxicity. Citation Format: Erika Ruiz-Garcia, Alicia Lopez-Yanez, Alette Ortega, Jorge Guadarrama-Orozco, Gisela Hernandez-Luis, Fabiola De la Rosa, Abelardo Meneses-Garcia, Horacio Astudillo-de la Vega. Next generation sequencing (NGS) of dihydropyrimidine dehydrogenase (DPYD) gene in Mexican patients with gastrointestinal (GI) carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3173.

RationaleAcute kidney injury (AKI) is a frequent complication in critically ill cancer patients.ObjectivesTo assess plasma neutrophil gelatinase-associated lipocalin (NGAL) levels and risks factors associated with AKI and mortality.MethodsWe recruited 96 critically ill cancer patients and followed them prospectively. Plasma NGAL levels were determined at intensive care unit (ICU) admission and at 48 hours. We generated receiver operating characteristic curves to assess the ability of NGAL to predict AKI. Logistic regression analysis was performed to determine risks factors associated with AKI. Cox-regression analysis was performed to evaluate 6-month mortality.Measurements and main resultsFrom 96 patients, 60 (63%) developed AKI and 33 (55%) were classified as stages 2 and 3. In patients without AKI at admission, plasma NGAL levels revealed an area under the curve (AUC) = 0.522 for all AKI stages and an AUC = 0.573 for stages 2 and 3 AKI (85% sensitivity and 67% specificity for a 50.66 ng/mL cutoff). We identified sequential organ failure assessment (SOFA) score (without renal parameters) at admission as an independent factor for developing stages 2 and 3 AKI, and haemoglobin as a protective factor. We observed that metastatic disease, dobutamine use and stage 3 AKI were independent factors associated with 6-month mortality.ConclusionsIn our cohort of critically ill cancer patients, NGAL did not predict AKI. SOFA score was a risk factor for developing AKI, and haemoglobin level was a protective factor for developing AKI. The independent factors associated with 6-month mortality included metastatic disease, dobutamine use, lactate and stage 3 AKI.

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