Journal of the Association of Genetic Technologists最新文献

Objectives: Recent NGS studies in multiple myeloma identified in one step and with comparable high accuracy to the concurrent cytogenomic tests the characteristic IGH translocations and copy number abnormalities. In addition, NGS allowed detection of gene mutations. This unprecedented success of a comprehensive genomic analysis suggests the possibility of replacing the separate tests in current use (cytogenetics, FISH, SNPs microarray and mutation analysis) with a single more efficient NGS assay. Down the road, NGS appears to have the potential to improve routine patient care with the clinical application of a detailed genomic profile.

Objectives: We present the case of a 56-year-old male with myelodysplastic syndrome (MDS) whose bone marrow immunophenotype showed lower positivity for CD45 and positivity for CD34; 8.66% of this population also expressed partial positives for MPO, CD16, CD117, CD36, CD33, and CD71, as well as positives for CD13, HLA-DR, and CD11b. No alterations in the pattern of maturation were seen in CD13 vs CD16 and CD13 vs CD11b. An analysis of a population of mature lymphocytes revealed CD45 high CD3+ in 87.5% of cells, CD45 high CD19+ in 7.6% of cells, and 4.9% NK cells. These results are consistent with a myelodysplastic syndrome with an excess of blasts type 1. Chromosome analysis of the bone marrow revealed an abnormal karyotype with a t(1;6)(p12;p11.1) as well as deletion 5q and a ring 11 in 12 of the 20 metaphase cells examined. The t(1;6)(p12;p11.1) has not been reported in association with any particular hematological malignancy and provides further insight into the range of cytogenetic abnormalities in MDS.

Objectives: B-Acute lymphoblastic leukemia (B-ALL) is a malignant disease that arises from several cooperative genetic mutations in a single B-lymphoid progenitor, leading to altered blast cell proliferation, survival and maturation, and eventually the lethal accumulation of leukemic cells. B-ALL accounts for about 12% of all childhood and adult leukemias diagnosed in developed countries, and 60% of those diagnosed are patients younger than 20 years old. As the most common cancer in children (25% of all cases) with a peak incidence in patients between the ages of two and five years, with a second, smaller peak in the elderly, the factors predisposing children and adults to ALL remain largely unknown. Herein we present an eight-year-old male patient diagnosed with B-ALL. Chromosome studies of 20 G-banded metaphases of the bone marrow detected an abnormal male karyotype with loss of 9p [i(9)(q10)] and loss of 17p [der(17)(?::17q11.2->17p11.2::17p11.2->17qter)] within the context of a complex karyotype in eight metaphase cells. Four of these abnormal metaphases showed additional material of unknown origin on chromosome 12 at p11.2 [add(12)(p11.2)]. Metaphase FISH analysis was crucial to characterize such complex chromosomal abnormalities, underscoring the importance of molecular cytogenetics in characterizing complex karyotypes in this hematological malignancy.

Objectives: T-cell acute lymphoblastic leukemia (T-ALL) is a pervasive hematologic malignancy that arises from developmental and genetic abnormalities manifested in lymphoblasts belonging to the T-cell lineage. Responsible for 10-15% of pediatric acute lymphoblastic leukemia (ALL) and 25% of adult ALL patients, T-ALL is characterized not only by cytomorphic features, but also by the aberrant expression of specific genes critical to T-cell development. Such changes in the genome ultimately result in mutational and developmental cascades that alter the chromosomal constitution, the process of which are used to organize T-ALL cases into different subgroups according to specific gene expression signatures. Clinically, comprehensive categorizations are important in risk stratification, assessment, and treatment protocols. Notable genetic subgroups include that of TAL, TLX1, TLX3, HOXA, MYB, ETP and NKX2. Current research also recognizes phenotypic and immunologic categories, such as ALK-positive ALCL, ALK-negative ALCL, BIA ALCL, AITL, and PTCL, NOS, which has revolutionized our understanding of T-cell lymphoma. Furthermore, it has been suggested that most T-ALL patients present with abnormal NOTCH1 genes in addition to mutations involving the JAK-STAT signaling pathway. These abnormalities are associated with the regulatory malfunction of T-cell development as well as that of their respective tumor suppressors and oncogenes. While recent studies have revealed characteristic defects in T-ALL, the interactions between oncogenes and their tumor suppressors with leukemia development are not well known as the signaling pathways involved behind each genetic lesion have yet to be fully explored. Studies involving FISH, RT-PCR, aCGH, and NGS offer novel perspectives to potentially learn more about the pathogenesis and cytogenetics of T-ALL, a field that demands further attention and research.

Objectives: Acute myeloid leukemia (AML) is caused by the arrested differentiation and dysregulated proliferation of myeloid precursors. Many AMLs harbor genetic abnormalities which determine the molecular mechanisms of the disease and are associated with distinct clinical and pathological features, prognosis, and targeted therapies. We present a case of acute myeloid leukemia with t(6;9)(p23;q34.1) and review the classic clinical presentations and underlying pathogenesis of the disease.

Objectives: Acute myeloid leukemia (AML) with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP is an uncommon subtype of AML accounting for less than 0.5% of AML cases. AML with t(8;16)/KAT6A-CREBBP has characteristic clinical and pathologic features including disseminated intravascular coagulation (DIC), leukemia cutis, hemophagocytosis, monocytic or myelomonocytic differentiation, is frequently associated with therapy-related AML and has a poor prognosis. We present a classic case of AML with t(8;16)/KAT6A-CREBBP occurring in a patient with both a germline NF1 mutation and recent cytotoxic therapy for embryonal rhabdomyosarcoma.

Objectives: Lymphoplasmacytic lymphoma (LPL, previously termed lymphoplasmacytoid lymphoma) is an uncommon mature B-cell lymphoma usually involving the bone marrow and less commonly the spleen and/or lymph nodes. The majority of patients with LPL have a circulating monoclonal immunoglobulin M (IgM) that can lead to a hyperviscosity syndrome known as Waldenström macroglobulinemia (WM). Although LPL appears to be a sporadic disease in the majority of cases, a familial predisposition is present in some cases. The main chromosomal abnormalities are trisomy 12, trisomy 3, isochromosome 6p, and 14q rearrangements involving IgH among complex karyotypes. Herein, we present an 89-year-old male patient who presents with LPL involving 80% of the marrow cellularity with circulating lymphoma cells. Chromosomal analysis detected two unrelated abnormal clonal populations: one clone has trisomy 12 as the sole abnormality in the stimulated culture, while the other clone has a 13q deletion as the sole abnormality in the cells from the non-stimulated culture. Trisomy 12 is one of the most common abnormalities in B-CLL and it is associated with an intermediate prognosis. Deletions 13q have been identified in B-cell malignancies, non-Hodgkin's lymphomas (NHL), as well as myelodysplastic syndromes and chronic myeloproliferative neoplasms (Heim and Mitelman, 2015). Trisomy 12/13q- FISH slide was reviewed looking at the segmented cells. Fifty segmented cells were scored and a 13q- pattern was detected in 36% (18/50) of the cells suggesting that this finding (the 13q- clone) may be myeloid in origin. Clinicopathologic correlation of these results was recommended.

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.

Objectives: Interphase fluorescence in situ hybridization (FISH) cutoff values are calculated using various mathematical methods to determine whether abnormalities seen are at reportable (statistically significant) levels. However, for interphase FISH studies of samples obtained from oncology patients who have been transplanted or treated, these cutoff values may result in reporting a false negative result due to the small percentage of residual disease that falls below such a cutoff value. Failure to detect the rare abnormal cells may impact patient care and prognosis. For such situations, the two questions are: is the disease still present, and if so, how prevalent is it? The first question is qualitative and the second is quantitative. Traditionally, only the quantitative parameters have been used for determining reportability. Here we propose a method to account for both qualitative and quantitative evaluations of interphase FISH results.

Objectives: Interphase fluorescence in situ hybridization (FISH) cutoff values are calculated using various mathematical methods to determine whether abnormalities seen are at reportable (statistically significant) levels. However, for interphase FISH studies of samples obtained from oncology patients who have been transplanted or treated, these cutoff values may result in reporting a false negative result due to the small percentage of residual disease that falls below such a cutoff value. Failure to detect the rare abnormal cells may impact patient care and prognosis. For such situations, the two questions are: is the disease still present, and if so, how prevalent is it? The first question is qualitative and the second is quantitative. Traditionally, only the quantitative parameters have been used for determining reportability. Here we propose a method to account for both qualitative and quantitative evaluations of interphase FISH results.