Gastrointestinal stromal tumors (GISTs) are rare and current estimates range from 4,000 to 6,000 number of GIST cases in the USA annually. Imatinib, a tyrosine kinase inhibitor, has shown a survival benefit in GISTs, and the presence of KIT mutation status is predictive of response. The current case discusses rapidly progressive dyspnea and heart failure in an elderly male with metastatic GIST who was started on imatinib. Although reported as a rare and sporadic side effect of imatinib, the current case illustrates rapidity and the clinical significance of cardiotoxicity, with onset at 2 weeks.Cases of imatinib-induced cardiotoxicity can range from being mild ventricular dysfunction to overt heart failure. Prior to starting imatinib, our patient had a history of hypertension. He subsequently ended up developing heart failure as acknowledged by the echocardiogram (ECHO). In general, elderly with preexisting cardiovascular comorbidity are at greater risk. The goal in such situations is immediate discontinuation or reduction of the imatinib dosage. The case prompts for awareness of imatinib cardiotoxicity. Moreover, a pretreatment cardiac assessment along with monitoring throughout therapy is therefore advisable. Also, imatinib-induced cardiotoxicity should be differentiated from imatinib-associated fluid retention, in which ECHO findings can be normal. This case report raises the concern for accelerated cardiotoxicity profile of imatinib. Further prospective studies with multidisciplinary input are needed to establish this association further.

Alternative splicing is an epigenetic mechanism that plays a role in the development and function of antigen-specific lymphocytes. One such is the zinc-finger-RNA-binding-motif-and-serine/arginine-rich-2 (ZRSR2), which is clinically implicated in myelodysplastic syndrome and leukemia. Here, we present a case of a young male with myriad autoimmune conditions and adenocarcinoma of the colon in the setting of ZRSR2 mutation.A 28-year-old male with common variable immunodeficiency disease, atopic dermatitis, autoimmune gastroenteropathy, inflammatory polyarthropathy, primary bone marrow failure, colon cancer, and family history of Lynch syndrome was admitted to our hospital for an acute flare of autoimmune enteropathy secondary to subtherapeutic tacrolimus levels.He initially developed pancytopenia at the age of 26 years. Workup for HIV, hepatitis, cytomegalovirus, human-herpesvirus 6, parvovirus was negative. Partial thromboplastin time (PTT), international normalized ratio (INR), d-dimer, ferritin, iron profile, antinuclear antibodies (ANA) screen was unremarkable. Direct, indirect, and super-combs antibodies were undetectable. Chromosomal study for Fanconi-related chromosomal breakage and telomerase gene panel was negative. Flow cytometry did not reveal an abnormal clone. Bone marrow biopsy showed markedly hypocellular marrow with reduced trilineage hematopoiesis and 1% blasts with normal cytogenetics, immunohistochemistry, fluorescence in situ hybridization (FISH), and negative for myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria (PNH). Cincinnati inherited children's bone marrow transplant (BMT) panel was negative. He was diagnosed with aplastic anemia and was treated with antithymocyte globulin, cyclosporine, prednisone, and currently tacrolimus. At the age of 26 years, he was diagnosed with colon cancer. Immunohistochemistry was positive for MLH1, but the confirmatory genetic testing for Lynch syndrome was negative. He underwent total proctocolectomy and ileostomy and is currently in remission. Next-generation sequencing of bone marrow revealed a germline homozygous ZRSR2 mutation.ZRSR2 spliceosome mutations are more common in males as it's an X-linked gene. They are seen in myelodysplastic syndrome, leukemia, increased autoimmune phenomenon, and 35 cases of colon cancer associated with this mutation are reported. In the setting of aplastic anemia and lynch negative colon cancer, we suspect our patient could have aplastic anemia due to an autoimmune phenomenon, underlying common variable immunodeficiency disease (CVID), or the new ZRSR2 mutation could be playing a role. Further studies and research is warranted to determine its true association with the disease entities. The underlying contributing factor is ZRSR2 mutation.

BACKGROUND In the United States, primary brain tumors comprise 2% of all cancers with an alarming 5-year survival rate of 35% [1,2]. To aid histopathological diagnosis, genomic profiling of tumors using next generation sequencing (NGS) has allowed more accurate molecular subclassification of tumors and identification of novel, subtype specific therapies in management [3]. We present single institutional data of molecular gene profiles in patients with adult primary brain tumors. Understanding the genetic landscape of these tumors will help determine molecular targets for currently available drugs and open new avenues for further drug development [4]. METHODS We retrospectively reviewed all primary brain tumor patients seen at LSU Health Science Center Shreveport who underwent NGS from July, 2017 to July, 2019. After reviewing a total of 44 patient charts, 26 were identified to have all the data required for our analysis. Standardized genetic sequencing reports made by molecular pathologists were used. Genetic mapping was performed and descriptive analysis was done using Statistical Analysis System (SAS). RESULTS Demographic characteristics of our patients consist of 50% males, 15% African American with an average age of diagnosis 59. The histopathological types diagnosed include 65% glioblastoma-multiforme and others comprising of gliosarcoma, pilocytic astrocytoma, ganglioma, oligodendroglioma, anaplastic oligodendroglioma, anaplastic ganglioma, meningioma, hemangiopericytoma, and astroblastoma. In 23% of patients, the results of gene sequencing in addition to histopathology impacted the clinical management by improving subclassification and in identifying targetable mutations. 42% of our patients found to have targetable mutations. CONCLUSION In the era of precision oncology, targeted gene sequencing of adult primary brain tumors may aid in diagnosis beyond histopathology by identifying the genetic landscape of tumors and molecular targets for individualized therapies.

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