Journal of the Association of Genetic Technologists

Penile cancer, while relatively rare compared to other male malignancies, has seen an increased global incidence, with 36,068 new cases reported in 2020. This condition primarily affects regions with low human development indexes, notably India, China and Brazil. The mainstay of treatment is often partial or total penectomy, which has a profound impact on patients' emotional and social lives. Due to limited options for early diagnosis, non-surgical treatments, restricted healthcare funding and the negative consequences of mutilating surgeries, penile cancer is often considered a neglected disease...

Identifying therapy-related AML (t-AML) of newly diagnosed acute leukemias is of great interest. Development of t-AML can occur after cytotoxic chemotherapy and/or radiation. We report a case of t-AML with CBFB::MYH11 fusion in a patient with a distant history of treated stage IIIB nodular sclerosing Hodgkin's lymphoma. We present the clinical course of the patient and the methods used to detect and monitor the rearrangement. Core binding factor AML (CBF-AML) after exposure to treatment is considered to be a good prognostic marker...

The Nobel Prize in Physiology or Medicine for 2023 awarded to Dr. Katalin Karikó and Dr. Drew Weissman recognized their seminal discoveries in nucleoside modifications of messenger RNA that were pivotal to developing the first mRNA vaccines for clinical use in humans. These novel vaccines were key for prophylactic control of a pandemic caused by the new coronavirus SARS-CoV-2 that emerged abruptly in late 2019/early 2020. This breakthrough capped years of previous research in coronaviruses that included SARS- CoV and MERS-CoV associated with earlier human outbreaks, developments of more efficient formulations to deliver nucleic acids in vivo, and applications of a novel mRNA technology to generate a new generation of better vaccines cost-effectively...

A recent landmark study reported the value of next-generation sequencing (NGS) to uncover pathogenic abnormalities of clinical significance in patients with pediatric B-ALL enrolled in the UKALL2003 clinical trial (Schwab et al., 2023). NGS, as whole genome sequencing (WGS) or targeted NGS (t-NGS), was combined with previous data (cytogenetics, FISH and MLPA) from 351 pediatric patients with precursor B-ALL who lacked a defining genetic abnormality (B-other ALL). This integration of tests classified patients into 15 distinct subtypes, each one characterized by a specific abnormality...

Congenital neutropenia, defined by absolute neutrophil count (ANC) 2.5x109/L in infants, includes a variety of genotypic alterations that manifest with chronic immunodeficiency and, as a result, presents in infancy with recurrent infections. The gene that encodes neutrophil elastase, ELANE, has pathological variants yielding two distinct phenotypes: severe congenital neutropenia (SCN) and cyclic neutropenia (CyN). While SCN exhibits persistent pathologic ANC values, CyN exhibits pathologic ANC values in a patterned fashion which can recur in 21-day intervals...

A new study demonstrated the power of WGS to comprehensively and accurately profile the genetic abnormalities in cases of childhood B-ALL that were previously studied with standard cytogenetics, FISH and MLPA (Ryan et al., 2023). Two cohorts with a total of 210 patients were studied. One cohort carried cytogenetic abnormalities of known significance (n=38). The other cohort (n=172) lacked cytogenetic abnormalities detectable by standard methods (B-other ALL group), and was treated within the UKALL2003 clinical trial...

The latest study with whole genome sequencing (WGS) in pediatric B-ALL validated its use as a standalone test to detect underlying clinically significant genetic abnormalities (Rezayee et al., 2023). This was a retrospective molecular survey in bone marrows previously collected and stored from 88 patients who were enrolled in NOPHO trials. The testing was done through 150 bp paired-end WGS applied to a paired analysis of leukemia-germline samples (L-N) (n=64), and to the analysis of leukemia-only samples (L) (n=88)...

The ribosomal protein S14 (RPS14) gene located at 5q33 codes for a protein involved in ribosomal biogenesis. The RPS14 gene has a length of 5.9 kb of DNA comprising 5 exons and 4 introns. It is possible that RPS14 is involved in the formation of pre-RNA 18s, an intermediate RNA that serves for the formation of the 40S small subunit of the ribosome. RPS14 haploinsufficiency (HI) produces alterations in intermediate RNA levels (pre-RNA 30S/18SE/18S), which are found in del(5q) MDS. In addition, RPS14 haploinsufficiency results in the formation of the MDM2 (double minute mouse E3 ubiquitin ligase)-RP (ribosomal protein) complex that prevents the MDM2-p53 interaction, generating an accumulation of p53 levels...

B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common leukemias affecting the pediatric population. It represents ~25% of cancer diagnoses among children. Specific genetic changes predict the prognosis in B-ALL with recurrent genetic changes. Here we present a case report of a 20-year-old male with B-ALL. The patient presented with acute onset worsening upper extremity pain with pallor, weight loss, dizziness, fatigue, and abnormal complete blood count (CBC). Conventional cytogenetics showed a karyotype of 46,XY,add(9)(q13),i(9)(q10)[19]...

The Nobel Assembly at the Karolinska Institute awarded the 2022 Nobel Prize in Physiology or Medicine to Svante Pääbo (Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany). This award acknowledged his discoveries about the genomes of extinct hominins (Neandertal man and the Denisovans), the molecular genetic insights of human origin and evolutionary history, and the understanding of phylogenetic relationships between archaic hominins and modern humans. The scientific advances included detection of Neandertal and Denisovan DNA carried by modern humans due to past admixture events, which in turn stimulated active research about the functional and phenotypic significance of such archaic ancestry on non-disease and disease phenotypic features in modern populations...

Patients with Fanconi Anemia (FA) have an increased risk of developing myeloid malignancies, which often precede the diagnosis of FA. We describe a patient with non-specific clinical findings diagnosed with myelodysplastic syndrome (MDS) at 17 years of age. A pathogenic SF3B1 alteration was identified and prompted evaluation for a bone marrow failure syndrome. Chromosomal breakage testing demonstrated an increase in breakage and radial formation; a targeted FA molecular panel identified variants of unknown significance in FANCB and FANCM...

We present a case study of a 73-year-old female with a history of pancytopenia. The bone marrow core biopsy was suggestive of a myelodysplastic syndrome, unspecified (MDS-U). Chromosomal analysis of the bone marrow revealed an abnormal karyotype including gain of chromosomes 1, 4, 6, 8, 9, 19, and 20 in addition to loss of chromosomes 11, 13, 15, 16, 17, and 22. Also, additional material of unknown origin was found on 3q, 5p, 9p, 11p, 13p, 14p, and 15p; there were two copies of 19p, a deletion of 8q, and numerous unidentified rings and markers were present...

Objectives Disorders of sex development(DSD)can result in discordance between the chromosomal and anatomicand/orphenotypic sex of a patient. Reporting patients with uncommon karyotypes associated with DSD is important for clinical comparison of developmental outcomes, and management. Methods We describe three female patients with karyotypes resulting in DSD and the use of a combination of chromosomes and FISH techniques to identify potential causes. Results The first patient was mosaic for idic(Y) that was negative for SRY by FISH...

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a high-risk subtype of AML that has recently undergone significant reclassification. Proper classification requires the integration of clinical history and diagnostic studies including peripheral blood and bone marrow morphology, flow cytometry, cytogenetic and molecular studies. The latter have significant clinical and prognostic implications. We present a case of a 55-year-old male diagnosed with AML-MRC with a pathogenic variant in TP53 and amplification of KMT2A (MLL) without rearrangement...

B-cell acute lymphoblastic leukemia (B-ALL) can afflict both adult and pediatric patients and is characterized by a build-up of B lymphoblasts. Here we present a case of a 25-year-old male patient with a history of B-ALL. Ninety percent of the bone marrow revealed pancytopenia with sheets of B lymphoblasts consistent with the diagnosis of B-ALL for acute pre-B lymphoblastic leukemia. The immunophenotype also presented predominant immature precursor B lymphoid cells positive for CD19, CD10, CD34, CD58, CD38, CD9, and TdT...

The Janus Kinase 2 gene (JAK2) provides instructions for generating a protein that promotes the division and growth, or what is referred to as the proliferation, of cells. This generated protein relays signals in cells in order to promote cell growth, as well as help manage the count of white blood cells, red blood cells, and platelets that are generated within the bone marrow. Mutations and rearrangements of JAK2 are found in 3.5% of B-acute lymphoblastic leukemia (B-ALL) cases and in 18.9% of Down syndrome B-ALL patients, and are associated with a Ph-like ALL and a poor prognosis...

Chronic lymphocytic leukemia (CLL) is a malignancy identified by an increase in the number of lymphocytes in the blood. It is one of the most common adult leukemias. It is a heterogeneous clinical disease with changeable progression. Chromosomal aberrations play a significant role in predicting clinical outcomes and survival. Treatment strategies for each patient are determined by chromosomal abnormalities. Cytogenetic methods are sensitive procedures for detecting abnormalities in the genome. The aim of this study was to document the incidence of different genes and gene rearrangements in CLL patients by comparing conventional cytogenetic and fluorescence in situ hybridization (FISH) results and predicting their prognosis...

Noninvasive prenatal testing (NIPT) has become a widely used screening method to detect fetal aneuploidies using cell-free fetal DNA (cffDNA) obtained from maternal blood. It is noninvasive, highly sensitive and specific, and can be offered in the first trimester of pregnancy. Though the goal of NIPT is to detect abnormalities in fetal DNA, occasionally abnormalities are detected that are not attributable to the fetus. Tumor DNA is laden with abnormalities and, rarely, NIPT has detected occult malignancy in the mother...

Myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) primarily affects adults older than 50 years and confers a worse prognosis with a higher risk of transformation to acute myeloid leukemia (AML) compared to myelodysplastic syndrome (MDS) and MDS with excess blasts-1 (MDS-EB-1). In ordering diagnostic studies for MDS, cytogenetic and genomic studies are vital as they have significant clinical and prognostic implications for the patient. We present a case of a 71-year-old male diagnosed with MDS-EB-2 with a pathogenic loss-of-function TP53 variant and discuss presentation, pathogenesis, and the importance of thorough diagnostic testing through multiple modalities to accurately diagnose and subtype MDS...

A recent report described a novel use of CMA for the first time in dogs that uncovered three cases of constitutional aneuploidy among 2,053 purebred and mixed-breed dogs. This advance is very significant because cytogenetic analysis by traditional methods in domestic dogs is technically difficult and may not conclusively identify all the abnormalities. This success with CMA testing anticipates the potential to discover more cases of canine aneuploidies as this technology becomes part of routine clinical genetic testing...