Genes, Chromosomes & Cancer最新文献_第10页

The impact of an additional copy of chromosome 21 in B-cell precursor acute lymphoblastic leukemia 21 号染色体额外拷贝对 B 细胞前体急性淋巴细胞白血病的影响。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-12-12 DOI: 10.1002/gcc.23217

Femke M. Hormann, Eva J. Mooij, Marieke van de Mheen, H. Berna Beverloo, Monique L. den Boer, Judith M. Boer

{"title":"The impact of an additional copy of chromosome 21 in B-cell precursor acute lymphoblastic leukemia","authors":"Femke M. Hormann, Eva J. Mooij, Marieke van de Mheen, H. Berna Beverloo, Monique L. den Boer, Judith M. Boer","doi":"10.1002/gcc.23217","DOIUrl":"10.1002/gcc.23217","url":null,"abstract":"A common finding in pediatric B-cell precursor acute lymphoblastic leukemia (BCPALL) is that chromosome 21 is never lost and an extra chromosome 21 is often gained. This implies an important role for chromosome 21 in the pathobiology of BCPALL, emphasized by the increased risk of BCPALL in children with Down syndrome. However, model systems of chromosome 21 gain are lacking. We therefore developed a BCPALL cell line (Nalm-6, DUX4-rearranged) with an additional chromosome 21 by means of microcell-mediated chromosome transfer. FISH, PCR, multiplex ligation-dependent probe amplification, and whole exome sequencing showed that an additional chromosome 21 was successfully transferred to the recipient cells. Transcription of some but not all genes on chromosome 21 was increased, indicating tight transcriptional regulation. Nalm-6 cells with an additional chromosome 21 proliferated slightly slower compared with parental Nalm-6 and sensitivity to induction chemotherapeutics was mildly increased. The extra copy of chromosome 21 did not confer sensitivity to targeted signaling inhibitors. In conclusion, a BCPALL cell line with an additional human chromosome 21 was developed, validated, and subjected to functional studies, which showed a minor but potentially relevant effect in vitro. This cell line offers the possibility to study further the role of chromosome 21 in ALL.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801428","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}

引用次数: 0

Expanding the molecular landscape of undifferentiated sarcomas of bone with a novel EWSR1-SSX3 gene fusion 通过新型 EWSR1-SSX3 基因融合扩展骨未分化肉瘤的分子图谱。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-12-05 DOI: 10.1002/gcc.23215

Caterina Fumagalli, Ruth Orellana, Malena Ferré, Allan Gonzalez, Lluis Catasús, Tania Vázquez, Ana Sebio, Antonio López-Pousa, Jaume Llauger, Ana Peiró, Cristina R. Antonescu

{"title":"Expanding the molecular landscape of undifferentiated sarcomas of bone with a novel EWSR1-SSX3 gene fusion","authors":"Caterina Fumagalli, Ruth Orellana, Malena Ferré, Allan Gonzalez, Lluis Catasús, Tania Vázquez, Ana Sebio, Antonio López-Pousa, Jaume Llauger, Ana Peiró, Cristina R. Antonescu","doi":"10.1002/gcc.23215","DOIUrl":"10.1002/gcc.23215","url":null,"abstract":"Undifferentiated sarcomas characterized by a primitive monomorphic round to spindle cell phenotype and often non-specific immunoprofile remain difficult to subclassify outside molecular analysis. The increased application of RNA sequencing in clinical practice led to significant advances and discoveries of novel gene fusions that furthered our understanding and refined classification of otherwise undifferentiated neoplasms. In this study, we report an undifferentiated round to spindle cell sarcoma arising in the femur of a 34-year-old female. The round to spindle tumor cells were arranged in short fascicles, with focal rosette formation, within a hyalinized stroma. The tumor immunoprofile included diffuse reactivity for CD99, SATB2, and TLE1 and patchy positivity for Cyclin D1, Keratin AE1/AE3, synaptophysin, and chromogranin. Other markers, such as EMA, SMA, desmin, S100, ERG, and WT1, were negative. Fluorescence in situ hybridization analysis for EWSR1 gene alterations showed a break-apart signal and targeted RNA sequencing revealed an EWSR1::SSX3 gene fusion. The patient received neoadjuvant chemotherapy followed by surgery and subsequently relapsed in less than a year with lung metastasis. Larger series are needed to determine if this fusion defines a novel subset of undifferentiated tumors or represents a genomic variant of already existing primitive round cell sarcoma categories, such as Ewing sarcoma or synovial sarcoma.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487299","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}

引用次数: 0

Gene amplification in neoplasia: A cytogenetic survey of 80 131 cases 肿瘤中的基因扩增：对 80 131 个病例的细胞遗传学调查。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-12-05 DOI: 10.1002/gcc.23214

Nils Mandahl, Fredrik Mertens, Felix Mitelman

{"title":"Gene amplification in neoplasia: A cytogenetic survey of 80 131 cases","authors":"Nils Mandahl, Fredrik Mertens, Felix Mitelman","doi":"10.1002/gcc.23214","DOIUrl":"10.1002/gcc.23214","url":null,"abstract":"Gene amplification is a crucial process in cancer development, leading to the overexpression of oncogenes. It manifests cytogenetically as extrachromosomal double minutes (dmin), homogeneously staining regions (hsr), or ring chromosomes (r). This study investigates the prevalence and distribution of these amplification markers in a survey of 80 131 neoplasms spanning hematologic disorders, and benign and malignant solid tumors. The study reveals distinct variations in the frequency of dmin, hsr, and r among different tumor types. Rings were the most common (3.4%) sign of amplification, followed by dmin (1.3%), and hsr (0.8%). Rings were particularly frequent in malignant mesenchymal tumors, especially liposarcomas (47.5%) and osteosarcomas (23.4%), dmin were prevalent in neuroblastoma (30.9%) and pancreatic carcinoma (21.9%), and hsr frequencies were highest in head and neck carcinoma (14.0%) and neuroblastoma (9.0%). Combining all three amplification markers (dmin/hsr/r), malignant solid tumors consistently exhibited higher frequencies than hematologic disorders and benign solid tumors. The structural characteristics of these amplification markers and their potential role in tumorigenesis and tumor progression highlight the complex interplay between cancer-initiating gene-level alterations, for example, fusion genes, and subsequent amplification dynamics. Further research integrating cytogenetic and molecular approaches is warranted to better understand the underlying mechanisms of these amplifications, in particular, the enigmatic question of why certain malignancies display certain types of amplification. Comparing the present results with molecular genetic data proved challenging because of the diversity in definitions of amplification across studies. This study underscores the need for standardized definitions in future work.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487319","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}

引用次数: 0

Rethinking cancer initiation: The role of large-scale mutational events 重新思考癌症的起源:大规模突变事件的作用。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-11-11 DOI: 10.1002/gcc.23213

Amil Shah MDCM

{"title":"Rethinking cancer initiation: The role of large-scale mutational events","authors":"Amil Shah MDCM","doi":"10.1002/gcc.23213","DOIUrl":"10.1002/gcc.23213","url":null,"abstract":"Cancer initiation is revisited in light of recent discoveries in cancer pathogenesis. Of note is the detection of mutated cancer genes in benign conditions. More significantly, somatic clones, which harbor mutations in cancer genes, arise in normal tissues from early development through adulthood, but seldom do they transform into cancer. Further, clustered mutational events—kataegis, chromothripsis and chromoplexy—are widespread in cancer, generating point mutations and chromosomal rearrangements in a single cellular catastrophe. These observations are contrary to the prevailing somatic mutation theory, which states that a cancer is caused by the gradual accumulation of mutations over time. A different perspective is proposed within the framework of Waddington's epigenetic landscape wherein tumorigenesis is viewed primarily as a disruption of cell development. Cell types are defined by their specific gene-expression profiles, determined by the gene regulatory network, and can be regarded as attractor states of the network dynamics: they represent specific, self-stabilizing patterns of gene activities across the genome. However, large-scale mutational events reshape the landscape topology, creating abnormal “unphysiological” attractors. This is the crux of the process of initiation. Initiation primes the cell for conversion into a tumor phenotype by oncogenes and tumor suppressor genes, which drive cell proliferation and clonal diversification. This view of tumorigenesis calls for a different approach to therapy.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89717877","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}

引用次数: 0

A case of spindle cell rhabdomyosarcoma with a ZFP64::NCOA3 fusion ZFP64:：NCOA3融合的梭形细胞横纹肌肉瘤一例。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-10-31 DOI: 10.1002/gcc.23212

Ken-ichi Yoshida, Yoji Kukita, Harumi Nakamura, Toru Wakamatsu, Keiichiro Honma, Toshinari Yagi

引用次数: 0

Alternative genetic alterations of MYC, BCL2, and/or BCL6 in high-grade B-cell lymphoma (HGBL) and diffuse large B-cell lymphoma (DLBCL): Can we identify different prognostic subgroups? 高级别B细胞淋巴瘤（HGBL）和弥漫性大B细胞淋巴瘤中MYC、BCL2和/或BCL6的替代性遗传改变：我们能确定不同的预后亚组吗？

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-10-28 DOI: 10.1002/gcc.23211

Siska Blomme, Pascale De Paepe, Helena Devos, Jan Emmerechts, Sylvia Snauwaert, Barbara Cauwelier

{"title":"Alternative genetic alterations of MYC, BCL2, and/or BCL6 in high-grade B-cell lymphoma (HGBL) and diffuse large B-cell lymphoma (DLBCL): Can we identify different prognostic subgroups?","authors":"Siska Blomme, Pascale De Paepe, Helena Devos, Jan Emmerechts, Sylvia Snauwaert, Barbara Cauwelier","doi":"10.1002/gcc.23211","DOIUrl":"10.1002/gcc.23211","url":null,"abstract":"High-grade B-cell lymphoma (HGBL)/diffuse large B-cell lymphoma (DLBCL) with rearrangements (R) in MYC and BCL2 and/or BCL6 are correlated with poor prognosis. Little is known about the impact of other genetic alterations (gain (G) or amplification (A)) of these genes. The aim of the study was to investigate whether we can identify new prognostic subgroups. Fluorescence in situ hybridization (FISH) results from 169 HGBL/DLBCL were retrospectively categorized into: (1) concurrent MYC-R and BCL2-R and/or BCL6-R—samples with MYC-R and BCL2-R (+/− BCL6-R); n = 21, and HGBL/DLBCL with MYC-R and BCL6-R; n = 11; (2) concurrent R and G/A in MYC and BCL2 and/or BCL6 called “alternative HGBL/DLBCL”—samples with (n = 16) or without (n = 6) BCL2 involvement; (3) BCL2 and/or BCL6 alterations without MYC involvement (n = 35); (4) concurrent G/A in MYC and BCL2 and/or BCL6 without R (n = 25); and (5) “No alterations” (n = 55). Patients with HGBL/DLBCL-MYC/BCL2 and “alternative” HGBL/DLBCL (with BCL2 involvement) had significantly worse survival rates compared to the “no alterations” group. G/A of these genes in the absence of rearrangements did not show any prognostic significance. HGBL/DLBCL with MYC-R and BCL6-R without BCL2 involvement showed a better survival rate compared to HGBL/DLBCL-MYC/BCL2. According to immunohistochemistry, “double/triple” expression (DEL/TEL) did not show a significantly worse outcome compared to absent DEL/TEL. This study highlights the continued value of FISH assessment of MYC, BCL2, and BCL6 in the initial evaluation of HGBL/DLBCL with different survival rates between several genetic subgroups.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66783810","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}

引用次数: 0

Myxoid epithelioid smooth muscle tumor of the vulva: A distinct entity with MEF2D::NCOA2 gene fusion 外阴粘液上皮样平滑肌肿瘤：一个具有MEF2D:：NCOA2基因融合的独特实体。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-10-23 DOI: 10.1002/gcc.23209

Laura M. Warmke, Amin Mustafa, Ying S. Zou, Jessica L. Davis, Thomas M. Ulbright, Sheila E. Segura

{"title":"Myxoid epithelioid smooth muscle tumor of the vulva: A distinct entity with MEF2D::NCOA2 gene fusion","authors":"Laura M. Warmke, Amin Mustafa, Ying S. Zou, Jessica L. Davis, Thomas M. Ulbright, Sheila E. Segura","doi":"10.1002/gcc.23209","DOIUrl":"10.1002/gcc.23209","url":null,"abstract":"Smooth muscle tumors are the most common mesenchymal tumors of the female genital tract, including the vulva. Since vulvar smooth muscle tumors are rare, our understanding of them compared to their uterine counterparts continues to evolve. Herein, we present two cases of morphologically distinct myxoid epithelioid smooth muscle tumors of the vulva with novel MEF2D::NCOA2 gene fusion. The tumors involved 24 and 37-year-old women. Both tumors presented as palpable vulvar masses that were circumscribed, measuring 2.8 and 5.1 cm in greatest dimension. Histologically, they were composed of epithelioid to spindle-shaped cells with minimal cytologic atypia and prominent myxoid matrix. Rare mitotic figures were present (1–3 mitotic figures per 10 high-power field (HPF)), and no areas of tumor necrosis were identified. By immunohistochemistry, the neoplastic cells strongly expressed smooth muscle actin, calponin, and desmin, confirming smooth muscle origin. Next-generation sequencing identified identical MEF2D::NCOA2 gene fusions. These two cases demonstrate that at least a subset of myxoid epithelioid smooth muscle tumors of the vulva represent a distinct entity characterized by a novel MEF2D::NCOA2 gene fusion. Importantly, recognition of the distinct morphologic and genetic features of these tumors is key to understanding the biological potential of these rare tumors.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49689969","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}

引用次数: 0

COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation COL1A1:：具有TERT启动子突变的PDGFB融合子宫肉瘤。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-10-23 DOI: 10.1002/gcc.23210

Yang Lu, Xinyi Chen, Wenjing Zeng, Ping Hua, Yangmei Shen, Yan Qiu, Xin He, Hongying Zhang

{"title":"COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation","authors":"Yang Lu, Xinyi Chen, Wenjing Zeng, Ping Hua, Yangmei Shen, Yan Qiu, Xin He, Hongying Zhang","doi":"10.1002/gcc.23210","DOIUrl":"10.1002/gcc.23210","url":null,"abstract":"COL1A1::PDGFB fusion uterine sarcoma is a rare uterine mesenchymal tumor with some clinicopathological features that overlap with those of soft tissue dermatofibrosarcoma protuberans. However, the varied clinicopathologic and genetic characteristics have not been fully revealed, which may be a potential pitfall for diagnosis. Here, we present a case of COL1A1::PDGFB fusion-positive uterine sarcoma in a 49-years-old female. Histologically, the tumor from the initial marginal excision predominantly exhibited high-grade fibrosarcomatous and myxofibrosarcoma-like appearances, while a low-grade focal area displaying storiform growth was identified in the residual tumor after subsequently extended resection. Immunohistochemically, the high-grade components mainly exhibited focal positivity for CD34 and mutated-type p53 immunoreactivity, whereas the low-grade component showed diffuse positivity for CD34 and wild-type p53 staining. The COL1A1::PDGFB fusion was confirmed by fluorescence in situ hybridization and next-generation sequencing. In addition, the TERT-124 C > T mutation was further identified in this lesion's fibrosarcomatous and classic storiform components. To the best of our knowledge, this is the first described case of COL1A1::PDGFB fusion uterine sarcoma with a TERT promoter mutation, which might be a novel genetic finding associated with tumorigenesis of this rare tumor.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49689968","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}

引用次数: 0

When molecular outsmarts morphology: Malignant ossifying fibromyxoid tumors masquerading as osteosarcomas, including a novel CREBZF::PHF1 fusion 当分子胜过形态学时：恶性骨化性纤维黏液样肿瘤伪装成骨肉瘤，包括一种新型CREBZF:PHF1融合。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-10-11 DOI: 10.1002/gcc.23206

Aarti E. Sharma, Josephine K. Dermawan, Andy E. Sherrod, Shefali Chopra, Robert G. Maki, Cristina R. Antonescu

{"title":"When molecular outsmarts morphology: Malignant ossifying fibromyxoid tumors masquerading as osteosarcomas, including a novel CREBZF::PHF1 fusion","authors":"Aarti E. Sharma, Josephine K. Dermawan, Andy E. Sherrod, Shefali Chopra, Robert G. Maki, Cristina R. Antonescu","doi":"10.1002/gcc.23206","DOIUrl":"10.1002/gcc.23206","url":null,"abstract":"We present two cases of malignant ossifying fibromyxoid tumor (OFMT) which eluded diagnosis due to compelling clinicopathologic mimicry, compounded by similarly elusive underlying molecular drivers. The first is of a clavicle mass in a 69 year-old female, which histologically showed an infiltrative nested and trabeculated proliferation of monomorphic cells giving rise to scattered spicules of immature woven bone. Excepting SATB2 positivity, the lesion showed an inconclusive immunoprofile which along with negative PHF1 FISH led to an initial diagnosis of high-grade osteosarcoma. Next generation sequencing (NGS) revealed a particularly rare CREBBP::BCORL1 fusion. The second illustrates the peculiar presentation of a dural-based mass in a 52 year-old female who presented with neurologic dyscrasias. Sections showed a sheeted monotonous proliferation of ovoid to spindle cells, but in contrast to Case #1, the tumor contained an exuberance of reticular osteoid and woven bone deposition mimicking malignant osteogenic differentiation. NGS showed a novel CREBZF::PHF1 fusion. Both tumors recurred locally less than 1 year post-operatively. As such we reiterate that careful morphologic examination is axiomatic to any diagnosis in our discipline, but this paradigm must shift to recognize that molecular diagnostics can provide closure where traditional tools have notable limitations.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41198903","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}

引用次数: 0

Colibactin mutational signatures in NTHL1 tumor syndrome and MUTYH associated polyposis patients NTHL1肿瘤综合征和MUTYH相关息肉病患者的大肠杆菌素突变特征。

IF 3.7 2区医学

Genes, Chromosomes & Cancer Pub Date : 2023-10-05 DOI: 10.1002/gcc.23208

D. Terlouw, A. Boot, Q. R. Ducarmon, S. Nooij, M. A. Jessurun, M. E. van Leerdam, C. M. Tops, A. M. J. Langers, H. Morreau, T. van Wezel, M. Nielsen

{"title":"Colibactin mutational signatures in NTHL1 tumor syndrome and MUTYH associated polyposis patients","authors":"D. Terlouw, A. Boot, Q. R. Ducarmon, S. Nooij, M. A. Jessurun, M. E. van Leerdam, C. M. Tops, A. M. J. Langers, H. Morreau, T. van Wezel, M. Nielsen","doi":"10.1002/gcc.23208","DOIUrl":"10.1002/gcc.23208","url":null,"abstract":"Polyketide synthase (pks) island harboring Escherichia coli are, under the right circumstances, able to produce the genotoxin colibactin. Colibactin is a risk factor for the development of colorectal cancer and associated with mutational signatures SBS88 and ID18. This study explores colibactin-associated mutational signatures in biallelic NTHL1 and MUTYH patients. Targeted Next Generation Sequencing (NGS) was performed on colorectal adenomas and carcinomas of one biallelic NTHL and 12 biallelic MUTYH patients. Additional fecal metagenomics and genome sequencing followed by mutational signature analysis was conducted for the NTHL1 patient. Targeted NGS of the NTHL1 patient showed somatic APC variants fitting SBS88 which was confirmed using WGS. Furthermore, fecal metagenomics revealed pks genes. Also, in 1 out of 11 MUTYH patient a somatic variant was detected fitting SBS88. This report shows that colibactin may influence development of colorectal neoplasms in predisposed patients.","PeriodicalId":12700,"journal":{"name":"Genes, Chromosomes & Cancer","volume":"63 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/gcc.23208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41173104","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}

引用次数: 0