Journal of the Association of Genetic Technologists最新文献_第3页

The Confirmatory Diagnostic Value of Whole Genome Sequencing (WGS) as a Standalone Test for Childhood B-cell ALL: The Results of a NOPHO Trials Cohort. 全基因组测序(WGS)作为儿童b细胞ALL的独立检测的确认性诊断价值:NOPHO试验队列的结果

Journal of the Association of Genetic Technologists Pub Date : 2023-01-01

Jaime Garcia-Heras

{"title":"The Confirmatory Diagnostic Value of Whole Genome Sequencing (WGS) as a Standalone Test for Childhood B-cell ALL: The Results of a NOPHO Trials Cohort.","authors":"Jaime Garcia-Heras","doi":"","DOIUrl":"","url":null,"abstract":"Objectives: 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 results demonstrated a full concordance between both WGS approaches and between the results from WGS and previous standard of care tests (SOCTs). All the mandatory aberrations that require testing in the current ALLTogether trial protocol were identified in 38 patients. In addition, WGS accurately identified the majority of aberrations characteristic of B-other ALL (35/36 cases), copy number abnormalities (CNAs) in eight critical genes or regions, CNAs that characterize the IKZF1plus profile, and the abnormalities in patients with Down syndrome. An adapted methodology was necessary for the detection of DUX4::IGH rearrangements in four patients. A comparison between sequencing coverages of 90X and 30X demonstrated that a lower 30X coverage was sufficient to detect all the relevant abnormalities. This successful testing was accomplished through filtering of WGS data focusing on just genes and genomic regions that are routinely implicated in pediatric B-ALL. As a result, it simplified the extraction of data and facilitated the interpretation of results. Overall, the precise identification of abnormalities that was accomplished by WGS allowed the assignment of patients to distinct genetic subtypes. The conclusion of this study was that WGS is quite reliable and can replace the use of SOCTs to profile pediatric B-ALL.","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138483584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Groundbreaking Validation of Whole Genome Sequencing (WGS) for a Comprehensive Genetic Profiling of Childhood B-cell ALL. 全基因组测序(WGS)对儿童b细胞ALL的全面遗传谱的开创性验证。

Journal of the Association of Genetic Technologists Pub Date : 2023-01-01

Jaime Garcia-Heras

{"title":"The Groundbreaking Validation of Whole Genome Sequencing (WGS) for a Comprehensive Genetic Profiling of Childhood B-cell ALL.","authors":"Jaime Garcia-Heras","doi":"","DOIUrl":"","url":null,"abstract":"Objectives: 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 WGS approaches used were a tumor-normal (T-N) pipeline and a tumor-only (T-only) pipeline. Most patients (202/210) carried a distinct abnormality already known or a new one that defined a genetic subtype. WGS identified almost all the abnormalities in the cohort with typical cytogenetic abnormalities previously detected (37/38 in the T-only pipeline, 34/38 in the T-N pipeline). The B-other ALL cohort showed two types of abnormalities by WGS. Some were cytogenetic abnormalities emblematic of B-ALL that were missed by previous standard methods (19/172 cases) due to poor samples or incomplete testing at the time of diagnosis. The remaining abnormalities were cryptic (145/153 cases) and defined genetic subtypes. Some new molecular variants emerged with WGS, the profile of PAX5 rearrangements and the ETV6::RUNX1-like subtype was characterized in more detail, and the detection of DUX4 rearrangements was markedly improved by a novel bioinformatic pipeline. Whole transcriptome sequencing (WTS) conducted in a subset of 85 patients was consistent with the results of WGS and standard cytogenomic techniques. This study validated the diagnostic use of WGS to uncover and characterize in detail the genetic aberrations in pediatric B-ALL. As a result, Ryan et al. endorsed the routine use of WGS to discover more abnormalities of clinical significance that define new genetic subtypes, as well as to improve diagnosis, risk stratification, and therapy.","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138483585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Isochromosome 9q: A Rare Event in Pediatric B-ALL. 同工染色体9q:儿童b型all的罕见事件。

Journal of the Association of Genetic Technologists Pub Date : 2023-01-01

Babu Sruthi, Tahmeena Ahmed, Rodrigo Hurtado, Ann-Leslie Berger-Zaslav, Daniel Tully, Htien Lee, Gabriela Evans, Cynthia Poerio, Carlos A Tirado

{"title":"An Isochromosome 9q: A Rare Event in Pediatric B-ALL.","authors":"Babu Sruthi, Tahmeena Ahmed, Rodrigo Hurtado, Ann-Leslie Berger-Zaslav, Daniel Tully, Htien Lee, Gabriela Evans, Cynthia Poerio, Carlos A Tirado","doi":"","DOIUrl":"","url":null,"abstract":"Objectives: 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]. DNA FISH analysis performed on the bone marrow showed hemizygous deletion of the 9p21(CDKN2A) in 15.5% of the nuclei examined. The presence of an isochromosome 9q [i(9)(q10) is a rare event in pediatric B-ALL. An isochromosome 9q occurs in 0.6% of the patients studied in the literature. The significance of this abnormality in pediatric B-ALL is not clear. Profiling cases like this to understand the molecular mechanisms of rare chromosomal abnormalities and rare mutations in children with B-ALL could help us to better treat them.","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiple Myeloma Detected by Noninvasive Prenatal Testing. 无创产前检查检测多发性骨髓瘤。

Journal of the Association of Genetic Technologists Pub Date : 2023-01-01

Katherine A Devitt, Juli-Anne Gardner

引用次数: 0

Cytogenetic Heterogeneity in Chronic Lymphocytic Leukemia. 慢性淋巴细胞白血病的细胞遗传学异质性。

Journal of the Association of Genetic Technologists Pub Date : 2023-01-01

Pina J Trivedi, Dharmesh M Patel, Mahnaz Kazi, Priya Varma

{"title":"Cytogenetic Heterogeneity in Chronic Lymphocytic Leukemia.","authors":"Pina J Trivedi, Dharmesh M Patel, Mahnaz Kazi, Priya Varma","doi":"","DOIUrl":"","url":null,"abstract":"Objectives: 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. Materials and Methods A total of 23 CLL patients, 18 men and five women with ages ranging from 45-75 years were enrolled in this case series. Interphase fluorescent in situ hybridization (I-FISH) was conducted on peripheral blood or bone marrow samples, whichever were available, and were cultured in growth culture medium. I-FISH was used to detect chromosomal abnormalities such as 11q-, del13q14, 17p-, 6q- and trisomy 12 in CLL patients. Results FISH results showed that there were different chromosomal gene rearrangements including del13q, del17p, del6q, del11q, and trisomy 12. Recurrent chromosomal abnormalities involved trisomy 12, del17p, del13q and novel translocation (8;17) were only seen in one patient. Conclusion Genomic aberrations in CLL are important independent predictors of disease progression and survival. Interphase cytogenetic analysis using FISH revealed chromosomal changes in the majority of CLL samples and is superior to standard karyotype analysis for identifying cytogenetic abnormalities.","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9083132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A B-ALL Pediatric Patient with a Cryptic IGH Rearrangement Within the Context of a Complex Karyotype. 一个B-ALL儿童患者与一个复杂核型背景下的隐性IGH重排。

Journal of the Association of Genetic Technologists Pub Date : 2023-01-01

Carlos A Tirado, Sheila Dobin, Krystal Eastwood, M Teresa Guardiola, Rodrigo Hurtado, Ari Rao

{"title":"A B-ALL Pediatric Patient with a Cryptic IGH Rearrangement Within the Context of a Complex Karyotype.","authors":"Carlos A Tirado, Sheila Dobin, Krystal Eastwood, M Teresa Guardiola, Rodrigo Hurtado, Ari Rao","doi":"","DOIUrl":"","url":null,"abstract":"Objectives: 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. Chromosome analysis of the bone marrow showed a complex karyotype described as 45~47,XY,i(8)(q10),der(10)add(10)(p11.1)add(10)(q23),-20,+1~2mar[cp3]/46,XY[36]. While IGH rearrangements were cryptic cytogenetically, DNA FISH analysis showed evidence of the IGH (14q32.2) gene rearrangement in 96.5% of the nuclei examined. These results were described as nuc ish(IGHx2)(5'IGH sep 3'IGHx1)[187/200],(5'IGH,3'IGH)x1~4(5'IGH con 3'IGHx0~2) [6/200]. The remaining probes were normal. Further studies using the MYC/IGH DC, DF probe from Abbott showed a gain of IGH signal in 7.5% of the nuclei examined: nuc ish(MYCx2,IGHx3)[15/200]. Metaphase FISH also showed that what appeared to be an isochromosome 8q was a derivative chromosome 8 defined as add(8)(p11.2) that contained a green IGH signal. In light of these results the karyotype was characterized as 45~47,XY,add(8)(p11.2),der(10)add(10)(p11.1)add(10)(q23),-20,+1~2mar[cp3].ish add(8) (p11.2) IgH+. IgH abnormalities are rare in B-ALL and are usually associated with a poor prognosis. However, at the present time our patient presented no evidence of persistent or residual disease and a cytogenetic response to the present therapy.","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9582083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

What's in a Name? The Many Classifications of Acute Myeloid Leukemia with Dysplasia. 名字里有什么?急性髓系白血病伴不典型增生的多种分类。

Journal of the Association of Genetic Technologists Pub Date : 2023-01-01

Nicholas C Taylor, Joanna L Conant, Juli-Anne Gardner

引用次数: 0

A CRLF2 Rearrangement in a Pediatric Patient with B-ALL Detected by FISH Within the Context of a Complex Abnormal Karyotype. 在复杂异常核型的背景下，FISH检测B-ALL儿童患者的CRLF2重排。

Journal of the Association of Genetic Technologists Pub Date : 2022-01-01

Carlos A Tirado, Yuri Lin, Ruby Tang, Aarushi Bajpai, Wilson Yeh, Sarvenaz Karamooz, Ari Rao

{"title":"A CRLF2 Rearrangement in a Pediatric Patient with B-ALL Detected by FISH Within the Context of a Complex Abnormal Karyotype.","authors":"Carlos A Tirado, Yuri Lin, Ruby Tang, Aarushi Bajpai, Wilson Yeh, Sarvenaz Karamooz, Ari Rao","doi":"","DOIUrl":"","url":null,"abstract":"Objectives: B-cell acute lymphoblastic leukemia (B-ALL) is one of the prevalent pediatric leukemias, accounting for 26% of cancers diagnosed in children 0-14 years of age. We present a case report of an 11-year-old girl with B-ALL. The patient was in complete remission nine months after diagnosis but passed away a month later from chemotherapy-induced hepatic failure, renal failure, and febrile neutropenia. Conventional cytogenetics showed a karyotype of 46,XX,del(5)(q31q35),add(6)(q23),del(7)(q32q36),add(11)(q23),ider(21)(q10)add(21) (q22),inc[20]. DNA FISH analysis performed on the bone marrow showed variant rearrangement of CRLF2, as well as loss of ETV6 signals and gain of RUNX1 signals. The presence of CRLF2 rearrangements within the context of a complex karyotype is often associated with CRLF2 overexpression and poor prognosis. The heterogeneity of B-ALL and the variability in the outcomes of patients that lack characteristic genetic abnormalities highlight the importance of profiling unusual genetic cases such as this one and continuing research to understand the molecular mechanisms of rarer mutations.","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35258637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mantle Cell Lymphoma Presenting with Cutaneous Lesions: A Rare Manifestation of a Systemic Disease. 以皮肤病变为表现的套细胞淋巴瘤:一种罕见的全身性疾病。

Journal of the Association of Genetic Technologists Pub Date : 2022-01-01

Nicholas Haslett, Deborah L Cook, Katherine A Devitt, Juli-Anne Gardner

引用次数: 0

Amplification of RUNX1 in a Patient With AML. AML患者RUNX1基因扩增

Journal of the Association of Genetic Technologists Pub Date : 2022-01-01

Rodrigo Hurtado, Stalin Tello, Juan Juarez, Carlos A Tirado

{"title":"Amplification of RUNX1 in a Patient With AML.","authors":"Rodrigo Hurtado, Stalin Tello, Juan Juarez, Carlos A Tirado","doi":"","DOIUrl":"","url":null,"abstract":"Objectives: Acute myeloid leukemia (AML) is a heterogeneous disease, characterized by clonal expansion of undifferentiated myeloid precursors, leading to alterations in hematopoiesis and bone marrow failure. Characteristic chromosomal abnormalities in AML are translocations t(8;21), inv(16), t(15;17), t(9;22), as well as mutations of genes that regulate proliferation and survival (FLT 3, PTPN 11, ETV 6/PDGFB), or genes responsible for differentiation and apoptosis (RUNX-1/RUNX1T1, PML/RARA, KMT2A, CEBPA and CBFB). Amplification of RUNX1 is a rare event in AML. Herein we described a 60-year-old patient that was admitted to the hospital due to a clinical picture of symptoms of acute anemia, thrombocytopenia, leukocytosis, and profuse nasal bleeding, hepatomegaly, splenomegaly, and gallstones. The blood cell count indicated the presence of 72% blasts. The bone marrow also showed 97% of blasts of myeloid lineage. The flow cytometry study also showed findings compatible with AML (MPOneg/+, CD34+, CD19neg /+d, CD117+, CD38neg /+, HLA-DR ++, CD13neg /+, CD33neg, CD15neg, D56neg, CD123+, CD7neg, CD11bneg, CD64neg, CD41aneg, which represented 68% of the pathological cellularity). Chromosome analysis showed additional copies of an isochromosome 21q. FISH studies revealed five copies of RUNX1. Amplification of RUNX1 is a rare event in AML with only a few cases reported in the literature (mainly therapy related AML) and it is usually associated with poor prognosis.","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40354797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0