Molecular ontogeny of donor-derived follicular lymphomas occurring after hematopoietic cell transplantation

The relative timing of genetic alterations that contribute to follicular lymphoma remains unknown. We analyzed a donor-recipient pair who both developed grade 2/3A follicular lymphoma 7 years after allogeneic transplantation and donor lymphocyte infusions. Both patients harbored identical BCL2/IGH rearrangements also present in 1 in 2,000 cells in the donor lymphocyte infusion, and the same V(D)J rearrangement, which underwent somatic hypermutation both before and after clonal divergence. Exome sequencing of both follicular lymphomas identified 15 shared mutations, of which 14 (including alterations in EP300 and KLHL6) were recovered from the donor lymphocyte infusion by ultra-deep sequencing (average read coverage, 361,723), indicating acquisition at least 7 years before clinical presentation. Six additional mutations were present in only one follicular lymphoma and not the donor lymphocyte infusion, including an ARID1A premature stop, indicating later acquisition during clonal divergence. Thus, ultrasensitive sequencing can map clonal evolution within rare subpopulations during human lymphomagenesis in vivo. SIGNIFICANCE: For the first time, we define the molecular ontogeny of follicular lymphoma during clonal evolution in vivo. By using ultrasensitive mutation detection, we mapped the time-course of somatic alterations after passage of a malignant ancestor by hematopoietic cell transplantation.     

The role of 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG PET) in diagnosis of ovarian cancer

We evaluated the clinical significance of ¹⁸F-FDG PET to detect malignant ovarian neoplasms and tumor spread. 40 patients (median age: 57.5 years) underwent laparotomy because of clinical suspicion of malignant ovarian tumors or recurrent disease. The results of the preoperatively performed PET were correlated with the postoperative histologic diagnosis and the intraoperatively assessed tumor spread. In 10 of 40 patients benign tumors were found, among which a tubo-ovarian abscess was the only one diagnosed as false positive. 4/30 malignant neoplasms did not originate from the coelomic epithelium, but all were correctly recognized as malignant tumors by PET, as was recurrent ovarian cancer in 12 patients. Out of 14 primary ovarian carcinomas, 2 borderline tumors and 1 well-differentiated adenocarcinoma FIGO stage I were not correctly identified. Considering the tumor type, sensitivity, and specificity were 90%, calculating for the positive and negative predictive value 96% and 75%, respectively, and 90% for the diagnostic accuracy. Those statistical parameters were slightly lower for PET detection of lymph node metastasis and peritoneal carcinomatosis. Although its diagnostic accuracy may vary depending on the clinical application, ¹⁸F-FDG PET is basically a suitable method for detecting ovarian malignancies, particularly in patients with relapsed ovarian carcinoma.