EPCO-29. GENOMIC PROFILING OF SPORADIC MULTIPLE MENINGIOMAS

INTRODUCTION In rare cases, sporadic meningiomas can occur as multiple tumors in the same patient without a known germline mutation. While the underlying mechanism that leads to the formation of these multiple lesions has been hypothesized to be monoclonal or independent, the genomic profiles to support these theories remain understudied. METHODS Patients with an absence of family history of meningioma and prior radiation history with multiple metachronous meningiomas were included. All tissue underwent whole exome sequencing and analysis of somatic single nucleotide variations (SNV), small insertion/deletion (INDEL) events together with copy number variations (CNV) was performed. The genomic findings were correlated with clinical data. RESULTS A cohort of 13 meningiomas and one dural specimen, from five individuals was studied. The majority (9/13 tumors) of tumors had NF2 mutation/Chr22 loss. Four out of 5 cases had a monoclonal origination, whereas one case displayed an independent clonal formation. The somatic profile of dura was unrevealing. In contrast to the current understanding, we found monoclonal formation of multiple meningiomas is not exclusive to NF2 driven cases, as non-NF2 mutated meningiomas can too display a monoclonal etiology. Moreover, multiple monoclonal-originating lesions did not always display a homogenous profile, but rather exhibited heterogeneity through branching evolution, where some lesions acquired genomic alterations associated with aggressive behavior. The histological characterization of multiple meningioma cases does not necessarily overlap with the genomic clustering. CONCLUSION To our knowledge, this is the first study to use unbiased comprehensive genomic methods to reveal the heterogeneity of multiple meningioma genomic profiles. Our extensive genomic characterization of this cohort revealed that monoclonal formation can be observed both in NF2 and non-NF2 mutant meningiomas and can introduce heterogeneity. Therefore, in order to understand the full scope of each individual’s disease, detailed genomic profiling of all lesions, when possible, should be performed.

EFFECTIVE TREATMENT FOR PRIMARY LOCALLY AGGRESSIVE INTERMEDIATE AND MALIGNANT SOFT TISSUE TUMOURS OF THE BREAST

OBJECTIVE This study aimed to examine the rare locally aggressive intermediate tumours and malignant primary breast mesenchymal tumours in the patients receiving surgical treatment. SUMMARY OF BACKGROUND DATA Locally aggressive intermediate tumours were subdivided into non-metastasising and rarely metastasising, while malignant group was subdivided as a single subgroup called able to metastasise. A retrospective examination of surgical notes and clinical charts was carried out reviewing gender, age, symptoms, duration of symptoms, tumour size, clinical presentation, radiation history, kind of surgery undergone, adjuvant radiotherapy, adjuvant chemotherapy, local recurrences, systemic metastases and mortality. RESULTS Mitotic index and Ki-67 were statistically different between locally aggressive and malignant groups (p ˂ 0.001). One local recurrence occurred in only one patient diagnosed as dermatofibrosarcoma protuberans among all patients. None of the entities showed distant metastasis or mortality. In this result, clear margin of surgery in locally aggressive intermediate group and combination of surgery with radiation therapy in the malignant group was the most important determinant for the prospect of the patients with mean follow up 28 months. CONCLUSION The main treatment for localised mesenchymal breast tumours is surgery. When the disease is locally advanced or malignant with high mitotic index, radiotherapy with surgery is predominantly used.Targeted therapies are promising with the limited place of chemotherapy.

Multiple meningiomas arising within the same hemisphere associated with Li-Fraumeni syndrome

Background: While meningiomas are some of the most common intracranial tumors, the presence of multiple ones at the time of presentation is rare and can most commonly be observed in patients with well-described syndromes (i.e., neurofibromatosis type 2) or those with prior cranial radiation history. In others, however, the pathophysiology remains unclear. Case Description: A 49-year-old female with no significant personal or familial oncologic medical history presented with a generalized seizure and was found to have ten meningiomas arising within the right hemisphere. She underwent a two-staged resection of all tumors, with pathology revealing the World Health Organization Grade I meningioma. Whole-exome sequencing revealed somatic NF2 mutations and heterozygous deletion of chromosome 22 overlapping with NF2, and analysis of the germline uncovered mutations of TP53, rendering a diagnosis of Li-Fraumeni Syndrome. Conclusions: This case represents a novel presentation of multiple meningiomas in a patient with newly diagnosed Li-Fraumeni syndrome, suggesting meningioma may be considered as part of this tumor-predisposed patient population.

UV-Mediated Photofunctionalization of Dental Implant: A Seven-Year Results of a Prospective Study

Our objective was to evaluate the seven-year results of photofunctionalized implants placed in regular, complex, and cancer-related cases. This study was a prospective, single-center study. Photofunctionalization was performed immediately prior to implantation with Ultraviolet (UV) light for 15 minutes. The success rate of each patient group and the influential factors on implant failure were analyzed. Seventy implants in 16 patients were included. Four implants were left submerged (sleep). The seven-year success rate of 30 implants in regular cases and 21 implants in complex cases was 100%. The success rate of 15 implants in cancer-related cases was 22.2%, in which implants were placed in resection or reconstructed sites with or without pre- or postoperative radiation history. Implant stability quotient (ISQ) values increased at second-stage surgery by 3.2 in regular cases and by 21.9 in complex cases, while it decreased by −3.5 in cancer cases. Multivariate analysis indicated that bone quality, location, and cancer resection significantly influenced implant failure. A very reliable seven-year success rate was obtained by UV-photofunctionalized implants in regular and complex cases, even with significant site-development procedures. However, the success rate in cancer cases was significantly and remarkably lower, suggesting remaining challenges of pathophysiologically compromised conditions, such as bone resection, segmental defect, and radiation.

Radiation history of Asian Asarum (sect. Heterotropa, Aristolochiaceae) resolved using a phylogenomic approach based on double-digested RAD-seq data

Background and Aims The genus Asarum sect. Heterotropa (Aristolochiaceae) probably experienced rapid diversification into 62 species centred on the Japanese Archipelago and Taiwan, providing an ideal model for studying island adaptive radiation. However, resolving the phylogeny of this plant group using Sanger sequencing-based approaches has been challenging. To uncover the radiation history of Heterotropa, we employed a phylogenomic approach using double-digested RAD-seq (ddRAD-seq) to yield a sufficient number of phylogenetic signals and compared its utility with that of the Sanger sequencing-based approach. Methods We first compared the performance of phylogenetic analysis based on the plastid matK and trnL–F regions and nuclear ribosomal internal transcribed spacer (nrITS), and phylogenomic analysis based on ddRAD-seq using a reduced set of the plant materials (83 plant accessions consisting of 50 species, one subspecies and six varieties). We also conducted more thorough phylogenomic analyses including the reconstruction of biogeographic history using comprehensive samples of 135 plant accessions consisting of 54 species, one subspecies, nine varieties of Heterotropa and six outgroup species. Key Results Phylogenomic analyses of Heterotropa based on ddRAD-seq were superior to Sanger sequencing-based approaches and resulted in a fully resolved phylogenetic tree with strong support for 72.0–84.8 % (depending on the tree reconstruction methods) of the branches. We clarified the history of Heterotropa radiation and found that A. forbesii, the only deciduous Heterotropa species native to mainland China, is sister to the evergreen species (core Heterotropa) mostly distributed across the Japanese Archipelago and Taiwan. Conclusions The core Heterotropa group was divided into nine subclades, each of which had a narrow geographic distribution. Moreover, most estimated dispersal events (22 out of 24) were between adjacent areas, indicating that the range expansion has been geographically restricted throughout the radiation history. The findings enhance our understanding of the remarkable diversification of plant lineages in the Japanese Archipelago and Taiwan.