Specific mosaic KRAS mutations affecting codon 146 cause oculoectodermal syndrome and encephalocraniocutaneous lipomatosis.

Oculoectodermal syndrome (OES) and encephalocraniocutaneous lipomatosis (ECCL) are rare disorders that share many common features, such as epibulbar dermoids, aplasia cutis congenita, pigmentary changes following Blaschko lines, bony tumor-like lesions, and others. About 20 cases with OES and more than 50 patients with ECCL have been reported. Both diseases were proposed to represent mosaic disorders, but only very recently whole-genome sequencing has led to the identification of somatic KRAS mutations, p.Leu19Phe and p.Gly13Asp, in affected tissue from two individuals with OES. Here we report the results of molecular genetic studies in three patients with OES and one with ECCL. In all four cases, Sanger sequencing of the KRAS gene in DNA from lesional tissue detected mutations affecting codon 146 (p.Ala146Val, p.Ala146Thr) at variable levels of mosaicism. Our findings thus corroborate the evidence of OES being a mosaic RASopathy and confirm the common etiology of OES and ECCL. KRAS codon 146 mutations, as well as the previously reported OES-associated alterations, are known oncogenic KRAS mutations with distinct functional consequences. Considering the phenotype and genotype spectrum of mosaic RASopathies, these findings suggest that the wide phenotypic variability does not only depend on the tissue distribution but also on the specific genotype.

Evaluation of the role of CT in the assessment of response to selective internal radiation therapy in patients with colorectal liver metastases.

Selective internal radiation therapy (SIRT) is a relatively new method for treating non-resectable liver tumours. There is reason to believe that conventional assessments of response by CT scan may underestimate the efficacy of this treatment. A study was undertaken in 54 patients to evaluate CT changes after SIRT for advanced colorectal cancer and to compare these with tumour marker (carcinoembryonic antigen (CEA)) changes to determine how best to assess whether a response has occurred. Computed tomography scans were carried out before treatment and at 3-monthly intervals thereafter. Serial CEA measurements were undertaken at 4-weekly intervals. Index lesions were identified and their size was assessed on serial scans by three independent, blinded investigators. Per cent changes in CEA levels after SIRT were calculated for all patients. Disappearance of all index lesions was noted in five patients (9.3%). A decrease in the size was seen in a further 41 patients (76%), no change was seen in five (9.3%), and an increase in size was noted in three (5.4%). The time taken for the maximum decrease in size to occur ranged from 3 to 21 months (median 12 months). Carcinoembryonic antigen changes were more dramatic, with a reduction of more than 75% within 2 months in 35 of 50 patients (70%) and a rise in only 3 of 50 patients (6%). Early assessment of response by CT scan may be misleading because of the time taken for size reduction to occur. Response to SIRT is more accurately judged in the early stages by tumour marker data.