RESUMO
In 2012, the Norwegian newborn screening program (NBS) was expanded (eNBS) from screening for two diseases to that for 23 diseases (20 inborn errors of metabolism, IEMs) and again in 2018, to include a total of 25 conditions (21 IEMs). Between 1 March 2012 and 29 February 2020, 461,369 newborns were screened for 20 IEMs in addition to phenylketonuria (PKU). Excluding PKU, there were 75 true-positive (TP) (1:6151) and 107 (1:4311) false-positive IEM cases. Twenty-one percent of the TP cases were symptomatic at the time of the NBS results, but in two-thirds, the screening result directed the exact diagnosis. Eighty-two percent of the TP cases had good health outcomes, evaluated in 2020. The yearly positive predictive value was increased from 26% to 54% by the use of the Region 4 Stork post-analytical interpretive tool (R4S)/Collaborative Laboratory Integrated Reports 2.0 (CLIR), second-tier biochemical testing and genetic confirmation using DNA extracted from the original dried blood spots. The incidence of IEMs increased by 46% after eNBS was introduced, predominantly due to the finding of attenuated phenotypes. The next step is defining which newborns would truly benefit from screening at the milder end of the disease spectrum. This will require coordinated international collaboration, including proper case definitions and outcome studies.
RESUMO
OBJECTIVES: Targeted therapies in non-small cell lung cancer (NSCLC) now also include inhibitors against mutated BRAF. We present clinicopathological characteristics of nearly one thousand unselected NSCLC patients tested for the targetable V600E/K BRAF-mutation. MATERIAL AND METHODS: NSCLC routinely tested for EGFR-mutations at Oslo University Hospital in the period February 2011-July 2013 were tested for V600E/K BRAF-mutations using a PCR-based method. RESULTS: We found a BRAF-mutation frequency of 1.7% in the total cohort of 979 patients, and 2.3% among 646 adenocarcinomas. One of the BRAF-positive samples was also KRAS-mutated, and one had an ALK-translocation. None of 231 squamous cell carcinomas were BRAF-mutated. The proportion of never-smokers among BRAF-positives was high (29%). CONCLUSION: BRAF-mutation analysis should be part of the subtyping of non-squamous NSCLC.
