Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach

Gene Mutation Profiles in Primary Diffuse Large B Cell Lymphoma of Central Nervous System: Next Generation Sequencing Analyses

The existence of a potential primary central nervous system lymphoma-specific genomic signature that differs from the systemic form of diffuse large B cell lymphoma (DLBCL) has been suggested, but is still controversial. We investigated 19 patients with primary DLBCL of central nervous system (DLBCL CNS) using the TruSeq Amplicon Cancer Panel (TSACP) for 48 cancer-related genes. Next generation sequencing (NGS) analyses have revealed that over 80% of potentially protein-changing mutations were located in eight genes (CTNNB1, PIK3CA, PTEN, ATM, KRAS, PTPN11, TP53 and JAK3), pointing to the potential role of these genes in lymphomagenesis. TP53 was the only gene harboring mutations in all 19 patients. In addition, the presence of mutated TP53 and ATM genes correlated with a higher total number of mutations in other analyzed genes. Furthermore, the presence of mutated ATM correlated with poorer event-free survival (EFS) (p = 0.036). The presence of the mutated SMO gene correlated with earlier disease relapse (p = 0.023), inferior event-free survival (p = 0.011) and overall survival (OS) (p = 0.017), while mutations in the PTEN gene were associated with inferior OS (p = 0.048). Our findings suggest that the TP53 and ATM genes could be involved in the molecular pathophysiology of primary DLBCL CNS, whereas mutations in the PTEN and SMO genes could affect survival regardless of the initial treatment approach

Determining spontaneous fission properties by direct mass measurements with the FRS Ion Catcher

We present a direct method to measure fission product yield distributions (FPY) and isomeric yield ratios (IYR) for spontaneous fission (SF) fragments. These physical properties are of utmost importance to the understanding of basic nuclear physics, the astrophysical rapid neutron capture process ('r process') of nucle-osynthesis, neutron star composition, and nuclear reactor safety. With this method, fission fragments are produced by spontaneous fission from a source that is mounted in a cryogenic stopping cell (CSC), thermalized and stopped within it, and then extracted and transported to a multiple-reflection time-of-flight mass-spectrometer (MR-TOF-MS). We will implement the method at the FRS Ion Catcher (FRS-IC) at GSI (Germany), whose MR-TOF-MS relative mass accuracy (similar to 10(-7)) and resolving power (similar to 600,000 FWHM) are sufficient to separate all isobars and numerous isomers in the fission fragment realm. The system's essential element independence and its fast simultaneous mass measurement provide a new direct way to measure isotopic FPY distributions, which is complementary to existing methods. It will enable nuclide FPY measurements in the high fission peak, which is hardly accessible by current techniques. The extraction time of the CSC, tens of milliseconds, enables a direct measurement of independent fission yields, and a first study of the temporal dependence of FPY distributions in this duration range. The ability to resolve isomers will further enable direct extraction of numerous IYRs while performing the FPY measurements. The method has been recently demonstrated at the FRS-ICr for SF with a 37 kBq Cf-252 fission source, where about 70 different fission fragments have been identified and counted. In the near future, it will be used for systematic studies of SF with a higher-activity Cf-252 source and a Cm-248 source. The method can be implemented also for neutron induced fission at appropriate facilities

Studying Gamow-Teller transitions and the assignment of isomeric and ground states at N=50

Direct mass measurements of neutron-deficient nuclides around the N = 50 shell closure below 100Sn were performed at the FRS Ion Catcher (FRS-IC) at GSI, Germany. The nuclei were produced by projectile fragmentation of 124Xe, separated in the fragment separator FRS and delivered to the FRS-IC. The masses of 14 ground states and two isomers were measured with relative mass uncertainties down to 1 x 10-7 using the multiple-reflection time-of-flight mass spectrometer of the FRS-IC, including the first direct mass measurements of 98Cd , 97Rh. A new QEC = 5437 +/- 67 keV was obtained for 98Cd, resulting in a summed Gamow-Teller (GT) strength for the five observed transitions (0+ --> 1+) as B(GT) = 2.94+0.32 -0.28. Investigation of this result in state-of-the-art shell model approaches accounting for the first time experimentally observed spectrum of GT transitions points to a perfect agreement for N = 50 isotones. The excitation energy of the long-lived isomeric state in 94Rh was determined for the first time to be 293 +/- 21 keV. This, together with the shell model calculations, allows the level ordering in 94Rh to be understood.(c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons .org /licenses /by /4 .0/). Funded by SCOAP3.Peer reviewe

Studying Gamow-Teller transitions and the assignment of isomeric and ground states at N = 50

Direct mass measurements of neutron-deficient nuclides around the N=50 shell closure below 100Sn were performed at the FRS Ion Catcher (FRS-IC) at GSI, Germany. The nuclei were produced by projectile fragmentation of 124Xe, separated in the fragment separator FRS and delivered to the FRS-IC. The masses of 14 ground states and two isomers were measured with relative mass uncertainties down to 1×10−7 using the multiple-reflection time-of-flight mass spectrometer of the FRS-IC, including the first direct mass measurements of 98Cd and 97Rh. A new QEC=5437±67 keV was obtained for 98Cd, resulting in a summed Gamow-Teller (GT) strength for the five observed transitions (0+⟶1+) as B(GT)=2.94−0.28+0.32. Investigation of this result in state-of-the-art shell model approaches accounting for the first time experimentally observed spectrum of GT transitions points to a perfect agreement for N=50 isotones. The excitation energy of the long-lived isomeric state in 94Rh was determined for the first time to be 293±21 keV. This, together with the shell model calculations, allows the level ordering in 94Rh to be understood