Genes, Chromosomes & Cancer最新文献

{"title":"“Benign” Metastasizing Fibrous Histiocytoma Harboring PRKCD Gene Fusions With Malignant Clinical Course","authors":"Charlotte I. Wang,&nbsp;Anne B. Giersch,&nbsp;Santiago Lozano Calderon,&nbsp;Edwin Choy,&nbsp;Fantine N. Giap,&nbsp;Yin P. Hung,&nbsp;G. Petur Nielsen,&nbsp;Ivan Chebib","doi":"10.1002/gcc.70094","DOIUrl":"10.1002/gcc.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>Dermatofibroma/fibrous histiocytoma is a common tumor of the dermis, composed of myofibroblasts, dendrocytes, and macrophages with characteristic entrapment of dermal collagen fibers at the periphery of the tumor. Various subtypes of dermatofibroma, including cellular, aneurysmal, and atypical dermatofibroma, are associated with an increased risk of recurrence, especially with incomplete excision. Two cases of benign fibrous histiocytoma with recurrence and metastasis are described. Patient 1 had a cellular fibrous histiocytoma with <i>KIRREL1</i>::<i>PRKCD</i> fusion presenting as a superficial and deep soft tissue mass involving the scapula and lateral clavicle. Patient 1 subsequently developed metastasis to the chest wall and thigh. Patient 2 had a recurrent aneurysmal fibrous histiocytoma with <i>LAMTOR1</i>::<i>PRKCD</i> fusion presenting as a large shoulder mass with invasion of the clavicle and lymph node metastasis. Patient 2 developed rapid local recurrence and PET-avid pulmonary nodules, radiologically consistent with metastasis. Fibrous histiocytoma is typically a morphologically benign neoplasm that only rarely exhibits clinically aggressive behavior with multiple recurrences and metastases. Although uncommon, recognition of this entity is important so that pathologists and sarcoma oncologists can ensure accurate diagnosis, multidisciplinary management, and appropriate clinical surveillance. In addition, complex chromosomal abnormalities may serve as useful indicators of fibrous histiocytoma with the risk of aggressive clinical behavior.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 11","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145549177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 107 Gene Nanostring Assay Effectively Translates the Cancer Genome Atlas, and Tumour Microenvironment Gastric Cancer Molecular Classification to a Patient-Derived Organoid Model","authors":"D. Skubleny,&nbsp;K. Purich,&nbsp;T. Williams,&nbsp;D. R. McLean,&nbsp;S. N. Martins-Filho,&nbsp;K. Buttenschoen,&nbsp;E. Haase,&nbsp;M. McCall,&nbsp;K. Baker,&nbsp;S. Ghosh,&nbsp;J. L. Spratlin,&nbsp;D. E. Schiller,&nbsp;G. R. Rayat","doi":"10.1002/gcc.70090","DOIUrl":"10.1002/gcc.70090","url":null,"abstract":"<p>There is a need to improve the translation of gastric cancer molecular classification schemes, such as those proposed by the Cancer Genome Atlas (TCGA) and Tumour Microenvironment score (TME), to clinical specimens and three-dimensional organoid culture models. In this study, we validate a 107-gene Nanostring assay informed by previously established machine learning models using a prospective cohort of gastric adenocarcinoma tumours and tumour-organoid pairs. Thirty-eight gastric adenocarcinoma specimens and twelve parent tumour-tumour organoid pairs were assigned TCGA and TME subtypes using gene expression measured by our custom Nanostring gene set. Subtypes were validated using gold-standard tests for Epstein–Barr virus (EBV) and microsatellite instability (MSI). Molecular subtype scores were compared to known clinicopathologic characteristics. The correlation between dose–response and molecular subtypes using an organoid drug assay and the Cancer Cell Line Encyclopedia (CCLE) was investigated. TCGA and TME subtypes were successfully applied to all specimens. The relationship of molecular subtype scores in our population compared to public cohorts was statistically identical for Lauren Class and Signet Ring status. Our method achieved 100% accuracy in labeling EBV and MSI subtypes. We identified 81.8% and 63.6% concordance between parent tumour-tumour organoid pairs for TME and TCGA subtypes, respectively. No significant correlation was identified between dose response to chemotherapy and molecular subtype scores. Analysis of the CCLE identified promising personalized therapy candidates for each molecular subtype. Our 107-gene Nanostring test successfully assigns TCGA and TME molecular subtypes to clinical tumour and tumour organoid samples for use in future study.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 11","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12612569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resurfacing Threats: Metastatic Ossifying Fibromyxoid Tumor Emerging After Almost Two Decades","authors":"Mario Ambros,&nbsp;Bernadette Liegl-Atzwanger,&nbsp;Karl Kashofer,&nbsp;Andreas Leithner","doi":"10.1002/gcc.70091","DOIUrl":"10.1002/gcc.70091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ossifying fibromyxoid tumor (OFMT) is an extremely rare mesenchymal tumor of uncertain differentiation having a potential for local recurrences and metastasis. OFMT can be classified as typical, atypical, and malignant tumors based on nuclear grade, cellularity, and mitotic rate. However, predicting the biological behavior remains challenging. We report one of these challenging cases of OFMT with metastases after 19 years. The primary tumor did not show morphologic characteristics of malignancy. We performed targeted RNA sequencing, copy number variation (CNV) analysis on all lesions and additional DNA methylation profiling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Presentation of the Case</h3>\u0000 \u0000 <p>Herein we report the case of a 66-year-old Caucasian female patient diagnosed in 2004 with an OFMT on her back that was surgically removed. In August 2023, the patient presented with two new soft tissue lesions in the right lower thigh and left gluteal area. Biopsy has been performed on both lesions. Pathology reports demonstrated an OFMT with an <i>EP400:PHF1</i> fusion. Both tumors were confirmed to represent the identical entity. Surgical removal of both tumors was performed with clear margins. The presence of late sequential metastases 19 years after initial resection of an OFMT, without any signs of malignancy after pathology review of the 2004 lesion was suggested. In December 2023, a potential fourth similar mass was detected with MRI and a full body PET-CT within the distal left semimembranosus muscle. A biopsy of this lesion has not been performed yet. It is currently being closely monitored through regular MRI examinations with contrast agents at intervals of 3 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case demonstrates the rare unpredictable potential of even typical OFMT to develop multiple soft tissue metastases after 19 years. Therefore, clinicians need to be aware of the metastatic potential of this tumor. Comprehensive and prolonged postoperative follow-up is necessary to track local recurrences and metastases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 11","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12612565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRAF7-Mutated Myxoid and Spindle Cell Mesenchymal Tumor Occurring in a Pediatric Patient in the Post-Transplant Setting: Expanding the Spectrum of TRAF7-Mutated Tumors","authors":"Stephanie Torres,&nbsp;Zachary High,&nbsp;Qian Wang,&nbsp;Clinton Piper,&nbsp;Erika Friehling,&nbsp;Brian Feingold,&nbsp;Ivy John,&nbsp;Marcus Malek,&nbsp;Armando Ganoza,&nbsp;John M. Skaugen,&nbsp;Catherine K. Gestrich","doi":"10.1002/gcc.70092","DOIUrl":"10.1002/gcc.70092","url":null,"abstract":"<div>\u0000 \u0000 <p><i>TRAF7</i> mutations have been reported in many tumor types, including subsets of meningiomas, mesothelioma, intraneural perineuriomas, and rare cases of aggressive fibromyxoid spindle cell tumors in adults. We expand the spectrum of <i>TRAF7</i>-mutated tumors by reporting a case of a <i>TRAF7</i>-mutated myxoid and spindle cell mesenchymal tumor in a 13-year-old female with a history of a heart and renal transplant. Histopathologic examination demonstrated hypocellular areas composed of bland spindle cells in a myxoid matrix and hypercellular areas with significant pleomorphism and up to 13 mitotic figures per 10 high-power fields. The spindle cells were positive for CD34 and negative for smooth muscle actin (SMA) and S100. Whole exome sequencing identified a <i>TRAF7</i> p.S561R mutation. Methylation profiling illustrated that the tumor did not embed within a distinct tumor group. The tumor was resected, and the patient remains stable at 7 months follow-up. This report is the first known case of a <i>TRAF7</i>-mutated myxoid and spindle cell tumor in a pediatric patient.</p>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 11","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Sweat Gland Adenocarcinoma of the Skin With ATL2::PRKD3 Fusion: A Potential Cutaneous Analog of Cribriform Adenocarcinoma of the Salivary Glands?","authors":"Anaïs Brunet,&nbsp;Barouyr Baroudjian,&nbsp;Maxence Mancini,&nbsp;Fanélie Jouenne,&nbsp;Baptiste Louveau,&nbsp;Isabelle Moulonguet,&nbsp;Amélie Osio,&nbsp;Samia Mourah,&nbsp;Maxime Battistella","doi":"10.1002/gcc.70093","DOIUrl":"10.1002/gcc.70093","url":null,"abstract":"<p>Many cutaneous adnexal tumors share molecular alterations with other homologous neoplasms occurring in salivary glands. Polymorphous adenocarcinoma (PAC) is a rare salivary gland tumor, usually associated with alterations in the <i>PRKD</i> gene family. In this report, we describe a primary cutaneous sweat gland adenocarcinoma of the scalp occurring in a 65-year-old female. Morphological features of the carcinoma were reminiscent of salivary gland PAC. Tumor cells were CK7+ S100+ SOX10+ p63 focally positive and p40-. Whole-transcriptome sequencing of the lesion showed the presence of an in-frame <i>ATL2::PRKD3</i> fusion. <i>PRKD1</i>, <i>2</i> or <i>3</i> fusions are characteristic of the cribriform subtype of PAC (cribriform adenocarcinoma of salivary gland, CASG). No past history of salivary gland tumor nor existing salivary gland tumor was retrieved in the patient. After complete excision of the tumor, the patient has been in complete remission for 17 months. This case suggests that a subset of adnexal adenocarcinomas of not otherwise specified type (NOS) may carry <i>PRKD</i> alteration and may constitute the cutaneous counterpart of salivary gland PAC/CASG. This finding argues in favor of a more systematic molecular exploration of adnexal adenocarcinomas NOS for better classification and prognosis.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 11","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12612566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel SMARCA2::DDIT3 Fusion in Primary Subcutaneous Myxoid Liposarcoma due to an Unusual Unbalanced Chromosomal Translocation","authors":"Ahmed Shah,&nbsp;William R. Sukov,&nbsp;Kevin Halling,&nbsp;Lukas Marcelis,&nbsp;Andre Oliveira","doi":"10.1002/gcc.70089","DOIUrl":"https://doi.org/10.1002/gcc.70089","url":null,"abstract":"<p>Myxoid liposarcoma (MLS) accounts for 20%–30% of all liposarcomas, with most cases harboring the fusion gene <i>FUS::DDIT3</i>, while approximately 5% exhibit the <i>EWSR1::DDIT3</i> fusion. We report the case of a 26-year-old male patient with a right upper arm mass. The tumor displayed the classic histological features of MLS, including small spindle/ovoid cells, variable univacuolated lipoblasts, and a prominent myxoid stroma with delicate arborizing vasculature. Despite these characteristic features, fluorescence in situ hybridization (FISH) revealed no apparent rearrangement of the <i>DDIT3</i> locus. Next-generation sequencing (NGS) identified a novel fusion transcript in which <i>SMARCA2</i> exon 4 was fused in-frame with <i>DDIT3</i> exon 2. Chromosomal microarray analysis demonstrated the unbalanced nature of the rearrangement, with partial deletions of 0.243 and 0.176 Mb flanking the centromeric end of the <i>DDIT3</i> locus on 12q13.3 (which also included <i>GLI</i>) and disrupting the <i>SMARCA2</i> locus on 9p24, respectively. The resultant chimeric fusion protein is predicted to lack the <i>SMARCA2</i> DNA-binding domains while retaining the <i>DDIT3</i> leucine zipper dimerization domain. These findings indicate an unusual and complex rearrangement, leading to the recruitment of a novel <i>DDIT3</i> partner gene. Moreover, they emphasize that the functional aspects of myxoid liposarcoma fusion genes depend on the retention of the key <i>DDIT3</i> domain. Finally, this case illustrates how classic morphology can appropriately trigger reflex molecular analyses, which may, in turn, uncover novel fusion genes or other molecular alterations.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70089","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Landscape of Pediatric Low-Grade Gliomas: Insights From RNA-NGS and Bioinformatic Analysis","authors":"Petr Brož,&nbsp;Martina Strnadová,&nbsp;Denisa Olejníková,&nbsp;Johana Kotiš,&nbsp;Tereza Pospíšilíková,&nbsp;Adéla Mišove,&nbsp;Miroslav Koblížek,&nbsp;Josef Zámečník,&nbsp;Michal Zápotocký,&nbsp;David Sumerauer,&nbsp;Aleš Vícha,&nbsp;Martin Kynčl,&nbsp;Petr Libý,&nbsp;Vladimír Beneš,&nbsp;Lenka Krsková","doi":"10.1002/gcc.70085","DOIUrl":"https://doi.org/10.1002/gcc.70085","url":null,"abstract":"<p>Pediatric low-grade gliomas (pLGG) are the most common group of childhood brain tumors. Genetic alterations in the RAS–RAF–mitogen-activated protein kinase (MAPK) pathway are the molecular drivers in the vast majority of pLGG. A large proportion of pediatric pLGG are characterized by the presence of fusion genes. An institutional molecular analysis together with an RNA-NGS study was performed to reveal LGG-associated molecular alterations. In our cohort of pLGG patients, molecular alterations were identified in 318 out of 342 cases (92.9%) through a combination of RT-PCR, Sanger sequencing, and NGS methodologies. Fusion events were independently called using three fusion callers: Archer Analysis 6.0 and/or 7.0, Arriba version 2.4, and STAR-Fusion 24. Among these, STAR-Fusion had the lowest sensitivity, detecting rearrangements in only 67% of fusion-positive cases. In contrast, Arriba detected rearrangements in 97.77% of cases, while Archer detected rearrangements in 88.6% of cases. These findings highlight differences in detection efficiency among fusion callers, emphasizing the importance of tool selection in molecular diagnostics. The detection of fusion genes is very important for correct diagnosis, prognosis, and adequate targeted treatment.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145272515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durable Response to Pazopanib (Tyrosine Kinase Inhibitor) in a Patient With EWSR1::CREM Gene Fusion Positive Intra-Abdominal Unclassified Epithelioid Sarcoma","authors":"Saba Shafi,&nbsp;Dan Jones,&nbsp;Xiaokang Pan,&nbsp;Marium Husain,&nbsp;Alan Rogers,&nbsp;Steve Oghumu,&nbsp;O. Hans Iwenofu","doi":"10.1002/gcc.70062","DOIUrl":"10.1002/gcc.70062","url":null,"abstract":"<p><i>EWSR1::CREM</i> fusion positive intrabdominal sarcomas defines a rare emerging group of aggressive mesenchymal neoplasms with a predilection for the celomic cavity and often manifesting perplexing immunophenotypic profile. There is no specific standard of care therapeutic option though anecdotal reports response to pazopanib have been reported. We report herein a case of a 62-year-old lady who presented with lower abdominal mass and pain. Right hemicolectomy performed showed a malignant epithelioid neoplasm. By immunohistochemistry, the tumor cells were positive for CD117, keratins, and mutation analysis was positive for <i>KIT</i> p.V5301 mutation, initially prompting a diagnosis of epithelioid gastrointestinal stromal tumor. However, the patient developed omental relapses while on imatinib and progressive disease persisted despite change to sunitinib. A re-review of the histopathology of both the hemicolectomy and relapsed omental sites showed marked cellular atypia, increased cellularity and mitosis in metastatic omental sites. By immunohistochemistry, the tumors in addition to CD117 positivity were also immunoreactive to keratins, synaptophysin, chromogranin, CD56, and MUC4. Next generation sequencing performed on both the primary and relapsed sites were positive for <i>EWSR1::CREM</i> gene fusion in addition to the <i>KIT. P.V5301</i> mutation. The tumor was then reclassified as <i>EWSR1::CREM</i> fusion positive intrabdominal unclassified epithelioid sarcoma with concomitant KIT mutation of unknown significance. The patient was treated with cytotoxic chemotherapy and radiation therapy with partial response, but treatment was stopped because of complications and lack of tolerance. Pazopanib as a single agent was then initiated, and patients have continued to respond for the past 7 months. We highlight the significant immunophenotypic heterogeneity in these tumors and perform an extensive review of the literature of this specific entity and broader group of <i>EWSR1::CREM/FUS</i> fusion positive tumors ranging from quasi-benign to malignant and finally we underscore the therapeutic utility of pazopanib as a single agent in this rare group of aggressive sarcomas.</p>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12515061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Spectrum of SRF-Rearranged Myoid Tumors: An Adult Case With SRF::SOHLH1 Fusion and Suspected Metastasis","authors":"Mohamed Elmoryah,&nbsp;Fatima B. Ergen,&nbsp;John M. Skaugen,&nbsp;Catherine K. Gestrich,&nbsp;Melissa A. Burgess,&nbsp;Kurt R. Weiss,&nbsp;Ivy John","doi":"10.1002/gcc.70086","DOIUrl":"10.1002/gcc.70086","url":null,"abstract":"","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytogenetic and Molecular Genetic Driven Prediction of Response to First-Treatment and Prognosis in Acute Myeloid Leukemia: A Retrospective Cohort Study","authors":"Henan Zhang,&nbsp;Xuan Liu,&nbsp;Xiaoning Wang,&nbsp;Qiang Zhang,&nbsp;Beibei Xin,&nbsp;Yiyang Shen,&nbsp;Pengcheng He,&nbsp;Jihong Zhang","doi":"10.1002/gcc.70081","DOIUrl":"https://doi.org/10.1002/gcc.70081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The first induction therapy is critical in determining subsequent treatment strategies and patient outcomes in acute myeloid leukemia (AML). This study aimed to comprehensively analyze the genetic landscape of AML patients to construct risk prediction models for the first-treatment response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 921 adult AML patients (Cohort 1) were included to characterize the genetic landscape and explore the correlations among genetic features in AML. To ensure the generalizability of the risk prediction models, 62 AML patients (Cohort 2) from another center were included in the modeling analysis. Risk prediction models for the first-treatment response were constructed using multivariable logistic regression with bootstrapping validation, and their impact on prognosis was also assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The cohort exhibited cytogenetic abnormalities, with favorable, intermediate, and adverse-risk features for 15.9%, 67.5%, and 16.5%, respectively. The top mutation genes were <i>NPM1</i>, <i>FLT3-ITD</i>, and <i>NRAS</i>. The top single nucleotide polymorphisms (SNPs) sites were <i>GATA2</i> rs2335052, <i>TP53</i> rs1042522, and <i>TET2</i> rs2454206. Risk assessment models showed that for the intensive chemotherapy group, <i>t</i>(16;16) (p13; q22), <i>CEBPA</i> bZIP in-frame, and <i>NPM1</i> type A were favorable factors, while trisomy 22, <i>TET2</i>, <i>FLT3-ITD</i>, <i>FLT3</i> p.D835, <i>ASXL1</i> rs750318549, and <i>TP53</i> were unfavorable factors. For the non-intensive chemotherapy group, normal karyotypes and all <i>CEBPA</i> mutations were favorable factors. Calibration curves revealed an area under the receiver operating characteristic curve (AUC) of 73.3% for the intensive chemotherapy cohort and 66.1% for the low-intensive chemotherapy cohort. Among non-transplanted patients, significantly longer overall survival (OS) and progression-free survival (PFS) were observed in those predicted to achieve complete remission (CR)/CR with incomplete count recovery (CRi) compared to those predicted to not achieve CR/CRi.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study first explores the combined role of karyotypes, mutations, and SNPs in AML treatment, offering valuable risk prediction models for guiding strategies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"64 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}