METHODS: Using as little as 20 ng of DNA from formalin-fixed paraffin-embedded tissues, we analysed 25 previously characterised gliomas for multi-locus copy number losses (CNLs) on 1p and 19q, including 11 oligodendrogliomas (ODG) and 14 non-oligodendroglial (non-ODG) controls. Fluorescence in-situ hybridisation (FISH) was used as a reference standard.
RESULTS: The software confidently detected combined contiguous 1p/19q CNLs in 11/11 ODGs (100% sensitivity), using a copy number cut-off of ≤1.5 and a minimum of 10 amplicons covering the regions. Only partial non-specific losses were identified in non-ODGs (100% specificity). Copy number averages of ODG and non-ODG groups were significantly different (p<0.001). NGS was concordant with FISH and was superior to it in distinguishing partial from contiguous losses indicative of whole-arm chromosomal deletion.
CONCLUSIONS: This commercial NGS panel, along with the standard Ion Torrent algorithm, accurately detected 1p/19q losses in ODG samples, obviating the need for specialised custom-made informatic analyses. This can easily be incorporated into routine glioma workflow as an alternative to FISH.
OBJECTIVE: This study aimed to investigate the effectiveness and safety of sulfonylurea therapy in Chinese NDM patients during infancy before genetic testing results were available.
METHODS: The medical records of NDM patients with their follow-up details were reviewed and molecular genetic analysis was performed. Sulfonylurea transfer regimens were applied in patients diagnosed after May 2010, and glycemic status and side effects were evaluated in each patient.
RESULTS: There were 23 NDM patients from 22 unrelated families, 10 had KCNJ11 mutations, 3 harbored ABCC8 mutations, 1 had INS mutations, 4 had chromosome 6q24 abnormalities, 1 had a deletion at chromosome 1p36.23p36.12, and 4 had no genetic abnormality identified. Sixteen NDM infants were treated with glyburide at an average age of 49 days (range 14-120 days) before genetic confirmation. A total of 11 of 16 (69%) were able to successfully switch to glyburide with a more stable glucose profile. The responsive glyburide dose was 0.51 ± 0.16 mg/kg/d (0.3-0.8 mg/kg/d), while the maintenance dose was 0.30 ± 0.07 mg/kg/d (0.2-0.4 mg/kg/d). No serious adverse events were reported.
CONCLUSIONS: Molecular genetic diagnosis is recommended in all patients with NDM. However, if genetic testing results are delayed, sulfonylurea therapy should be considered before such results are received, even in infants with newly diagnosed NDM.