Somatic genomic imbalances in 'tumour-free' surgical margins of oral cancer.

Up to 30% of oral squamous cell carcinoma (OSCC) patients develop local recurrence and distant metastasis. The molecular status of histologically cancer-free tumour margins could be a critical factor in predicting tumour behaviour. The aim of this study was to detect somatic genomic imbalances in OSCC with emphasis on the surgical margins. DNA was isolated from tumour tissues, margin tissues, and blood samples (used as control) obtained from 11 OSCC patients, and genome-wide array comparative genomic hybridization was performed. Imbalances were present in both tumours and margins, although, as expected, they were more prevalent in tumours (duplications, P = 0.0002; deletions, P = 0.0001). Duplications were more frequent than deletions in both tumours and margins, but without statistical significance. Fifteen imbalances in tumour tissues were recurrent and all of them were duplications. Four of these were found both in tumours and margins and involved chromosomes 1q, 8p, Xp, Yp, and Yq. Four imbalances were recurrent in margin tissue and all of them were duplications (autosomes 8 and 17 and both sex chromosomes). Histologically 'cancer-free' margins hide genomic alterations consistent with unexplained OSCC recurrences. Establishing the molecular status of the margins could improve outcome prediction.

Tacrolimus Therapeutic Drug Monitoring in Stable Kidney Transplantation and Individuation of CYP3A5 Genotype.

The posology of tacrolimus (TAC) is usually guided by its therapeutic drug monitoring. Some patients reach target concentrations (CTs) quickly, others more slowly. In a retrospective study, 20 kidney transplant recipients were included (mean age, 50.7 ± 14.1 years; weight 64.0 ± 14.2 kg; patients clinically stable for over a year). We studied cytochrome CYP3A5 genotype, in particular CYP3A5 6986A>G, the most important polymorphism related to the metabolism of TAC (wild genotype CYP3A5 *1 genotype, and CYP3A5 *3 variants). One year after transplantation, the CTs were 5.0 to 8.0 ng/mL. The patients were divided into group A (TAC doses < 6.0 mg/d) and group B (TAC doses > 6.0 mg/d). All were tested for the CYP3A5 gene sequence to characterize their polymorphism. Patients with CYP3A5 *1/*1 and *1/*3 were extensive metabolizers, and those with CYP3A5 *3/*3 were poor metabolizers. In group A and group B, the average TAC doses at the time of therapeutic drug monitoring were 3.0 ± 1.4 ng/mL (0.05 ± 0.03 mg/kg) and 12.8 ± 3.7 ng/mL (0.2 ± 0.1 mg/kg), respectively (P < .001). Group A was the poor metabolizers genotype, while in group B, the extensive metabolizers genotype was present. Patients with the CYP3A5 *1/*1 or *1/*3 genotype required 1.5 to 2 times higher doses than patients *3/*3 to reach CT. This genetic test allows clinicians to know, before the kidney transplant, the patient's TAC metabolism pattern and then to optimize the drug exposure.