A Patient with Myxoid/Round Cell Liposarcoma (MRCL) Involving the Well-known Translocation t(12;22): A Case Report with the Cytogenomic Landscape of this Rearrangement.

OBJECTIVES: Myxoid/Round Cell Liposarcoma (MRCL) is characterized as a soft tissue sarcoma that is associated with unusual patterns of metastasis to extrapulmonary sites, such as bones and other soft tissue sites. Here, we present a case of a 48-year-old male patient, diagnosed with MRCL. The patient presented with a grade 1 myxoid liposarcoma in his left leg. DNA FISH analysis showed variant rearrangements of the EWSR1 (22q12) gene and loss of the 5' DDIT3 (CHOP 12q13) gene. The variant rearrangement showed one or two fusions with multiple separated (rearranged) signals. The EWSR1-DDIT3 rearrangement has been reported in MRCL. The variant rearrangements of the EWSR1 (22q12) gene findings correlate with concurrent conventional cytogenetic findings and were described as nuc ish(EWSR1x2) (5'EWSR1 sep 3'EWSR1x1)[128/100],(5'EWSR1,3'EWSR1)x1~3(5'EWSR1 con 3'EWSR1x1~2)[57/100]. The variant rearrangements of the DDIT3 (CHOP 12q13) gene findings were described as nuc ish(5'DDIT3x1,3'DDIT3x2)(5'DDIT3 con 3'DDIT3x1)[195/200]. Molecular cytogenetic studies also showed a rearrangement of EWSR1 (22q12) in 64% of nuclei and variant rearrangement in 31.5% of nuclei. A loss of DDIT3's (12q13) 5' signal was found in 97.5% of interphase nuclei. Molecular pathology results indicated the patient was positive for EWSR1 (exon 7) and DDIT3 (exon 2) fusion. The patient underwent radiation therapy pre-resection of the myxoid liposarcoma. The most common form of MRCL is associated with t(12;16)(q13;p11), leading to FUS-CHOP and EWS-CHOP fusion proteins acting as aberrant transcription factors. The key element here is that this EWSR1-DDIT3 rearrangement led to a translocation t(12;22)(q13;q12) which is a rare cytogenetic event that led to the development of MRCL in this patient.

Amplification of CCND1 in Urothelial Carcinoma.

OBJECTIVES: Urothelial carcinoma (UC) is the most prevalent form of bladder cancer and a significant cause of mortality in the world each year. As molecular genetic techniques improve, researchers and medical professionals are turning toward finding potential biomarkers to diagnose and characterize UC, guide treatment decisions, and use as therapeutic targets. Located on chromosome 11q13.2, the CCND1 gene encodes Cyclin D1, a CDK-regulating protein that plays a critical role in cell cycle progression. Amplification of CCND1 is seen in about 10% of all bladder cancer patients and has been a target of research due to its potential as a prognostic biomarker and a therapeutic target. However, existing literature on CCND1 amplification and Cyclin D1 expression report conflicting information about their clinical significance and association with disease staging, pointing to the need for more research to determine mechanistic pathways. Additionally, while there are currently no approved therapies or drugs that directly target CCND1 or Cyclin D1 in UC, several clinical trials with drugs targeting CDK4/CDK6 in the Cyclin D1 pathway are already underway. This paper aims to provide an update on the amplification of CCND1 in urothelial carcinoma, including an overview of recent research on elucidated pathways, clinical significance, relevant therapies under development, and directions for future research.

Applications and Advancements of CRISPR/Cas9 Technology: An Update.

OBJECTIVES: The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is an RNA-guided DNA targeting platform widely known for its application in genome editing. Originally derived from the bacterial and archaebacterial defense mechanism against phage infection, it has since been studied and utilized for its potential as a genetic engineering tool and as a therapeutic agent. The Cas9 protein in its standard form induces double-stranded breaks (DSBs) in the target dsDNA sequence; however, modifications of the Cas9 protein have allowed for single-stranded breaks (SSBs) and even epigenetic modifications of gene expression. In comparison with previous methods including RNA interference, Zinc Finger Nucleases, and TAL Effector Nucleases, CRISPR is cheaper, more easily customized, and has a higher fidelity to its target site with fewer off-target effects. Consequently, CRISPR has become a central gene editing technique in a broad variety of research settings, with great potential for applications in human health. In this review, we offer an overview of CRISPR's mechanism of action and recent advancements in the application of CRISPR, as well as discuss literature pertinent to CRISPR applications to human health including many exciting prospective treatments for serious pathologies.

FISH is Still an Excellent Tool to Monitor High-Grade Lymphomas.

OBJECTIVES: A 61-year-old male patient whose core needle biopsies of tissue involved a malignant lymphoid infiltrate composed of intermediate to large cells positive for CD20, PAX5, CD10, BCL6, BCL2, and cMYC, and negative for MUM1. Mitotic activity was brisk with a correspondingly high index of proliferation by Ki67 (~95%) and the patient was diagnosed with a diffuse large B-cell lymphoma, germinal center phenotype. DNA FISH analysis was performed on the paraffin embedded tissue from the right external iliac lymph node using the LSI BCL6 (3q27) and MYC (8q24) dual color break apart probes from Cytocell and the LSI BCL2 (18q21) dual color break apart probe from Abbott. We found rearrangements of BCL6 in 95% of the cells examined, MYC rearrangements in 77% of the cells and BCL2 rearrangements in 95% of the nuclei. These findings allowed us to classify this case as a triple-hit lymphoma now called "high-grade B-cell lymphomas" with MYC, BCL2, and/or BCL6 rearrangements.