Cancer Genetics最新文献

{"title":"Brain abscesses, neutropenia, and B-ALL: Multiple testing modalities required to confirm PDCD10 and ETV6 dual diagnoses","authors":"Runjun D. Kumar ,&nbsp;Liesbeth Vossaert ,&nbsp;Weimin Bi ,&nbsp;Nichole Owen ,&nbsp;Rachel E. Rau ,&nbsp;Hannah L. Helber ,&nbsp;Ghadir Sasa ,&nbsp;Jacquelyn Reuther ,&nbsp;Angshumoy Roy ,&nbsp;Kevin E. Fisher","doi":"10.1016/j.cancergen.2024.08.001","DOIUrl":"10.1016/j.cancergen.2024.08.001","url":null,"abstract":"<div><p>Recognition of patients with multiple diagnoses, and the unique challenges they pose to clinicians and laboratorians, is increasing rapidly as genome-wide genetic testing grows in prevalence. We describe a unique patient with dual diagnoses of <em>PDCD10</em>-related cerebral cavernous malformations and <em>ETV6</em>-related thrombocytopenia with associated neutropenia. She presented with brain abscesses as an infant, which is highly atypical for these disorders in isolation. Confirming her diagnoses depended on thorough phenotyping both during and after her acute illness. Furthermore, the causative variant in <em>ETV6</em> is a novel single-exon deletion that required multiple modalities with manual review to confirm, including unique use of polymorphic nucleotides in trio exome data. She illustrates the special challenges of patients with multiple diagnoses, and the multiple tools clinicians and laboratorians must use to treat them.</p></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 5-9"},"PeriodicalIF":1.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focal cortical dysplasia type IIIb associated with a KRAS-mutant ganglioglioma","authors":"Elena A. Repnikova ,&nbsp;Lei Zhang ,&nbsp;Brent A. Orr ,&nbsp;Jennifer Roberts ,&nbsp;Timothy Zinkus ,&nbsp;Melissa Gener ,&nbsp;Alexander Kats","doi":"10.1016/j.cancergen.2024.07.004","DOIUrl":"10.1016/j.cancergen.2024.07.004","url":null,"abstract":"","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"288 ","pages":"Pages 1-4"},"PeriodicalIF":1.4,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141984898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"16. An evaluation of clinical significance of the TP53 polyadenylation signal-disrupting variant rs78378222-G","authors":"Dayo Shittu,&nbsp;Henoke Shiferaw,&nbsp;Tracey Ferrara,&nbsp;Anas Awan,&nbsp;Huan Mo","doi":"10.1016/j.cancergen.2024.08.018","DOIUrl":"10.1016/j.cancergen.2024.08.018","url":null,"abstract":"<div><div><em>TP53</em> germline pathogenic variants (Li-Fraumeni syndrome) and somatic mutations are important in tumorigenesis and tumor classifications. However, the clinical significance of the <em>TP53</em> polyadenylation signal-disrupting variant rs78378222-G remains unclear. To address this, we employed a dual approach.</div><div>First, we used All of Us Research Program data to evaluate its disease association with phenome-wide association studies (PheWAS). In the trans-ancestry PheWAS (n = 245,378, 3383 were heterozygous and &lt;20 were homozygous), the G-allele was significantly associated with uterine leiomyoma (OR = 1.75 [1.42-2.16]). In Blacks (n = 56,911, allele frequency [AF] = 0.00171), it was significantly associated with anal and rectal polyps (11.97 [4.46-32.07]), and nominally associated with hyperparathyroidism, head and neck cancer, and primary cardiomyopathies. In Whites (n = 133,572, AF = 0.0112), it was significantly associated with benign neoplasm of the uterus (1.61 [1.27-2.03]) and in Hispanics (n = 45,032, AF = 0.00276), with uterine leiomyoma (3.82 [2.11-6.84]).</div><div>Next, we imputed rs78378222 with microarray data from the Cancer Genomic Atlas (TCGA, overall carrier rate 1.9%). Adult glioma (GBMLGG) had the highest carrier rate for the G-allele (4.6% in IDH-wildtype and 3.2% in IDH-mutant). There was no evidence of differential prognosis or rates of <em>TP53</em> mutation/17p loss among carriers within the evaluated tumor types that had enough carriers for analysis.</div><div>Our preliminary analyses demonstrate that <em>TP53</em> rs78378222-G allele was consistently associated with higher risk of neoplasms and tissue overgrowth in multiple ancestry groups. However, its role in cancer classification and prognostication may be limited, necessitating further validation with more data.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S6"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"17. Intrachromosomal amplification of chromosome 21 as the sole chromosomal aberration in a primary AML patient","authors":"Leila Youssefian,&nbsp;Alden Huang,&nbsp;Sung-Hae L. Kang,&nbsp;Niroshini Senaratne,&nbsp;Thomas Lee,&nbsp;Fumin Lin","doi":"10.1016/j.cancergen.2024.08.019","DOIUrl":"10.1016/j.cancergen.2024.08.019","url":null,"abstract":"<div><div>Intrachromosomal amplification of chromosome 21 (iAMP21), is a rare but recurrent acquired clonal chromosome aberration observed in acute myeloid leukemia (AML), usually associated with chemoresistance and poor prognosis. The vast majority of AML patients with iAMP21 also present with a complex karyotype and <em>TP53</em> mutations, which are known markers for poor prognosis and interfere with understanding the clinical impact of iAMP21 in AML. We present a primary AML patient who had a bone marrow karyotype study showing additional material of unknown origin on 21q as the sole abnormality. The AML and high risk MDS FISH panel studies did not identify any abnormalities, including a normal signal pattern for <em>RUNX1</em>. Additional FISH studies for chromosome 21 detected five copies of the 21q22.13q22.2-specific signals on the derivative chromosome 21, suggestive of iAMP21. Chromosomal microarray analysis confirmed amplification of 21q, which included <em>ERG</em> and <em>ETS2</em> genes but not <em>RUNX1</em>. The hematologic malignancy NGS panel revealed <em>KIT</em> and <em>U2AF1</em> mutations. This 58-year-old male patient presented with pancytopenia and a hypercellular marrow with increased myeloblasts. This patient's disease was refractory to induction and salvage chemotherapy. While the clinical course showed similar chemoresistance as observed in other 21q-amplified AML, there is no concurrent <em>TP53</em> aberration or complex karyotype observed in this case. This case demonstrates that iAMP21 may be an early driver for AML tumorigenesis, and these results implicate <em>ERG</em> and/or <em>ETS2</em> instead of <em>RUNX1</em> as the critical gene(s) of iAMP21 in AML. Further characterization of iAMP21 in AML and may provide opportunities for alternative therapies.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S6"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"8. Reduced subclone diversity in clonal cytopenia of undetermined significance compared to myelodysplastic syndrome","authors":"Sridhar Nonavinkere Srivatsan ,&nbsp;Monique Chavez ,&nbsp;Christopher Miller ,&nbsp;Andrew Menssen ,&nbsp;Ajay Khanna ,&nbsp;Catrina Fronick ,&nbsp;Robert Fulton ,&nbsp;Sharon Heath ,&nbsp;Constantine Logothetis ,&nbsp;Tasha Burton ,&nbsp;Victoria Donaldson ,&nbsp;Claudia Cabrera ,&nbsp;Ravi Vij ,&nbsp;Eric Duncavage ,&nbsp;Jin Shao ,&nbsp;Raya Saba ,&nbsp;Megan Jacoby ,&nbsp;Matthew J. Walter","doi":"10.1016/j.cancergen.2024.08.010","DOIUrl":"10.1016/j.cancergen.2024.08.010","url":null,"abstract":"<div><div>Clonal cytopenias of undetermined significance (CCUS) is a precursor state to myelodysplastic syndrome (MDS), a blood cancer, and is distinguished solely on the absence of morphologic dysplasia, which has diagnostic variability. Determining differences in clonal architecture (total number and size of clones) may provide an objective assessment of disease status. We hypothesized that CCUS patients will have reduced molecular disease burden with fewer subclones compared to MDS patients suggesting that MDS is at higher risk of progressing to secondary acute myeloid leukemia (sAML). We performed whole genome sequencing with higher exome coverage (eWGS) on bone marrow (n=58) or peripheral blood (n=4) and paired normal DNA from baseline banked samples from patients with CCUS (n=13), MDS (n=29), and sAML (n=20) to define clonal architecture. While the median number of total validated somatic mutations per sample was not different between CCUS, MDS, and sAML, the median variant allele frequency of the dominant clone was lower in CCUS (21.3%) compared to MDS (39.2%, p&lt;0.05) and sAML (45.2%, p&lt;0.001). Additionally, the proportion of patients without subclones was higher for CCUS (5/13 [38.5%]) compared to MDS and sAML (4/29 [13.8%] and 0/20 [0%], respectively, p ≤ 0.0006), suggesting that CCUS samples have reduced subclonal diversity compared to MDS. The data suggest that leveraging clonal architecture and subclonal diversity in the evaluation of patients with low blood counts could provide an objective measure to characterize and monitor disease burden in CCUS and MDS, and potentially assess risk of sAML progression, rather than relying on dysplasia alone.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S3"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"9. Best practices for testing and reporting of FISH studies in multiple myeloma: Recommendations from the CGC working group","authors":"Xinyan Lu ,&nbsp;Erica F. Andersen ,&nbsp;Rahul Banerjee ,&nbsp;Celeste C. Eno ,&nbsp;Patrick R. Gonzales ,&nbsp;Angela M. Lager ,&nbsp;Patricia M. Miron ,&nbsp;Trevor Pugh ,&nbsp;Fabiola Quintero-Rivera ,&nbsp;Virginia C. Thurston ,&nbsp;Daynna J. Wolff ,&nbsp;Jian Zhao ,&nbsp;Linda B. Baughn","doi":"10.1016/j.cancergen.2024.08.011","DOIUrl":"10.1016/j.cancergen.2024.08.011","url":null,"abstract":"<div><h3>Purpose</h3><div>Multiple myeloma (MM) remains an incurable plasma cell malignancy with recurrent primary and secondary cytogenetic abnormalities having prognostic and therapeutic implications. Fluorescence in situ hybridization (FISH) is the gold-standard assay to detect these genetic abnormalities. However, FISH testing for MM is heterogeneous among clinical laboratories, with differences in plasma cell isolation, FISH panel design, and reporting practices.</div></div><div><h3>Methods</h3><div>The CGC Plasma Cell Neoplasm workgroup conducted a survey targeting the international MM clinician community on utilization of FISH and result reporting/interpretation.</div></div><div><h3>Results</h3><div>There were 102 survey responses representing 14 countries. Most (74%) MM clinicians utilize their own in-house FISH testing service with 81% reporting plasma cell enrichment was performed by their lab. 90% of respondents desired FISH at diagnosis, 72% during disease progression and 40% for treatment/response assessment. The most-requested FISH probes included: TP53 (99%), t(4;14) (92%), 1q gain/amplification (91%), t(14;16) (90%), t(11;14) (85%), t(14;20) (76%), 1p deletion (67%), while FISH for ploidy status, deletion 13q/-13, t(6;14), MYC rearrangement, and other rare IG rearrangements were ranked lower in importance (10-50%). About 40% of respondents were dissatisfied with clarity, summary, and interpretation of FISH reports. When challenged to interpret a FISH report, only 2% of responders interpreted results correctly and the majority were either unsure or misinterpreted the report.</div></div><div><h3>Conclusion</h3><div>Our study showed that significant improvements are needed by clinical lab directors in MM FISH report clarity to benefit both the clinician and patient. We propose standardization of best MM FISH practices and reporting.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Pages S3-S4"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"75. Copy number variation heterogeneity as the measure for biological consistency in hierarchical cancer classifications","authors":"Ziying Yang,&nbsp;Paula Carrio-Cordo,&nbsp;Michael Baudis","doi":"10.1016/j.cancergen.2024.08.077","DOIUrl":"10.1016/j.cancergen.2024.08.077","url":null,"abstract":"<div><div>Cancers are heterogeneous diseases with unifying features of abnormal and consuming cell growth, where the deregulation of normal cellular functions is initiated by the accumulation of genomic mutations in cells of - potentially - any organ. At diagnosis malignant tumors present with patterns of somatic genome variants on diverse levels of heterogeneity. Among the different types of genomic alterations, copy number variants (CNV) represent a distinct, near-ubiquitous class of structural variants. Cancer classifications such as the National Cancer Institute Thesaurus (NCIt) provide large sets of hierarchical cancer classification vocabularies and promote data interoperability and ontology-driven computational analysis.</div><div>However, high heterogeneity in cellular phenotypes and dynamic plasticity of tumor microenvironments make tumor categorization a demanding and complicated task with the need to balance between categorical classifications and individual, 'personalized' feature definitions. To find out how categorical classifications reflect biological facts, we conducted a meta-analysis of inter-sample genomic heterogeneity at different levels of the classification hierarchies based on genome-spanning CNV profiles from 97,142 individual samples across 512 hierarchical cancer entities in the progenetix database. The use of a large data set of individual cancer samples allows for a greater exploration of genomic tumor heterogeneity between and inside given diagnostic concepts. With this study, we applied hierarchical clustering to quantify the heterogeneity among cancer entities through a refined measure of hamming dissimilarity based on CNV events. The results point out common/specific CNV patterns and potential subtypes of cancer entities, which will help in the improvement of patient stratification and current cancer classification.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S24"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2. Diagnostic next generation sequencing to detect MYD88 L265P in lymphoplasmacytic lymphoma compared to ddPCR","authors":"Lauren M. Wainman ,&nbsp;Guohong Huang ,&nbsp;Donald C. Green ,&nbsp;Eric Y. Loo ,&nbsp;Prabhjot Kaur ,&nbsp;Parth Shah ,&nbsp;Jeremiah Karrs","doi":"10.1016/j.cancergen.2024.08.004","DOIUrl":"10.1016/j.cancergen.2024.08.004","url":null,"abstract":"<div><div>Lymphoplasmacytic lymphoma (LPL) is a B-cell lymphoproliferative disorder characterized by bone marrow infiltration of lymphoplasmacytic cells. Studies have identified <em>MYD88</em> L265P mutation as a diagnostic marker to distinguish LPL from other small B-cell lymphomas (e.g. marginal zone lymphoma, chronic lymphocytic leukemia). However, detection rates for this mutation have varied depending on the analytic methodology, with data suggesting that routine Next Generation Sequencing (NGS) does not demonstrate the required sensitivity to reliably detect <em>MYD88</em> L265P. NGS has become a work-horse of the modern genetic laboratory by basketing multiple single-gene assays into one multiplexed assay. In several routine cases, visual observation using IGV demonstrated <em>MYD88</em> L265P variants in cases of suspected LPL with low tumor content. To study this, we performed droplet digital PCR (ddPCR) and our routine NGS for <em>MYD88</em> L265P in a cohort of 35 cases of lymphoid neoplasms (25 LPL, 6 CLL, 4 negative bone marrow cases). Our standard NGS method achieved an average depth of ∼535 reads across this region. We utilized manual review and BAMtools to assess <em>MYD88</em> L265P in NGS cases. Limit of detection for ddPCR was determined to be 0.3% variant allele frequency (VAF) with 10ng DNA input. <em>MYD88</em> L265P VAF detection by NGS and ddPCR was comparable down to 0.5% VAF (R²=0.968). Setting an appropriate threshold for detection based on ddPCR results resulted in zero NGS false positives. This study demonstrates that NGS can be a sensitive and reliable method for detection of <em>MYD88</em> L265P with adequate coverage and specific assessment parameters.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S1"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"59. What the TERT? - A telomerase reverse transcriptase case study","authors":"Yeshmira Moodley,&nbsp;Longqian Yang,&nbsp;Bronwyn Neumann,&nbsp;Amanda Dixon-McIver","doi":"10.1016/j.cancergen.2024.08.061","DOIUrl":"10.1016/j.cancergen.2024.08.061","url":null,"abstract":"<div><div>Telomerase reverse transcriptase is a catalytic subunit of the telomerase protein that is involved in the maintenance of genomic stability. <em>TERT</em> aberrations are important biomarkers in the diagnosis, prognosis, and treatment of many human cancers. The <em>TERT</em> promoter has proven to be a difficult region of testing amongst a variety of currently available technologies.</div><div><em>TERT</em> promoter mutation analysis was performed on brain tissue of a 62-year old male meningioma patient using MALDI-TOF (Agena Bioscience MassARRAY platform) and detected a low frequency <em>TERT</em> mutation. The pathologist questioned the result and sent some of the sample for additional testing to 2 different referral laboratories - one aliquot was sent for Pyrosequencing and the other for NGS - both with a higher limit of detection than MALDI-TOF. Neither methodology detected a <em>TERT</em> mutation. On the basis of these result the diagnosis was changed.</div><div>Certain of our <em>TERT</em> mutation, an aliquot of the remaining extracted DNA was sent for digital droplet PCR (ddPCR) which has the same limit of detection as our MALDI-TOF platform. A <em>TERT</em> mutation was confirmed.</div><div>This case highlights the challenges in <em>TERT</em> promoter mutation analysis as well as the significance of confirmatory testing. The importance of confirming results using platforms with an appropriate limit of detection is paramount in reducing under-reporting of low level mutations of clinical significance.</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S19"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"66. Prognostic impact of genomic testing results in patients undergoing transplantation for myelofibrosis","authors":"Xiaoyu Qu ,&nbsp;Emily Stevens ,&nbsp;Matt Fitzgibbon ,&nbsp;Lan Beppu ,&nbsp;Tim M. Monahan ,&nbsp;Cecilia C.S. Yeung ,&nbsp;Derek L. Stirewalt ,&nbsp;David Wu ,&nbsp;Jerald Radich ,&nbsp;H. Joachim Deeg ,&nbsp;Min Fang","doi":"10.1016/j.cancergen.2024.08.068","DOIUrl":"10.1016/j.cancergen.2024.08.068","url":null,"abstract":"<div><div>Despite its known superior detection rate for chromosomal anomalies compared to karyotype and FISH studies, Chromosome Genomic Array Testing (CGAT) is not used as a routine clinical test for myelofibrosis. We investigated the prognostic significance of CGAT and mutation results by NGS in myelofibrosis patients who underwent hematopoietic cell transplantation between 2000 and 2017 at our center (n=44). CGAT was done in a CLIA lab using CytoScanHD (ThermoFisher). NGS was performed either in a CLIA lab using UW Heme Gene Panel by NGS (n=9) or retrospectively at a research lab using TruSight myeloid panel (Illumina, n=35). Twenty-four patients (55%) had abnormal CGAT results. In 18 patients (41%), CGAT uniquely demonstrated cnLOH, with 9p cnLOH being the most frequent (n=8, 18%). Thirty-five patients had myeloproliferative neoplasm (MPN) driver mutations: 17 (39%) <em>JAK2</em> pV617F, 16 (36%) <em>CALR</em> exon 9 mutation, and two <em>MPL</em> pW515 (5%). With a median of 91 (range 2-258) months of follow-up, event-free survival (EFS; event referring to relapse) was 59%, and overall survival (OS) was 68%. Abnormal CGAT results (n=24, P=0.03), <em>U2AF1</em> mutation (n=5, P=0.028) and 1q gain (n=3, P=0.009) were associated with worse EFS. The genetic aberrations had no significant effect on OS in this cohort. <em>ASXL1</em> mutations (n=14) appeared to associate with a later onset of chronic graft-versus-host-disease (P=0.03). In conclusion, assessments by both CGAT and NGS pre-transplantation provide valuable outcome information and may be considered as routine clinical testing for myelofibrosis</div></div>","PeriodicalId":49225,"journal":{"name":"Cancer Genetics","volume":"286 ","pages":"Page S21"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}