更新于：2024-11-01

RMI1

更新于：2024-11-01

基本信息

别名

BLAP75、BLM-associated protein of 75 kDa、C9orf76

+ [5]

简介

Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability.

关联

项与 RMI1 相关的药物

PIP-199

靶点

FANCM x RMI1 x RMI2

作用机制

FANCM抑制剂 [+2]

在研机构

The University of Sydney

原研机构

The University of Sydney

在研适应症

Bloom综合征 [+1]

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 RMI1 相关的临床结果

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100 项与 RMI1 相关的转化医学

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0 项与 RMI1 相关的专利（医药）

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151

项与 RMI1 相关的文献（医药）

2024-10-01·The Lancet Oncology

Risk-prediction models in postmenopausal patients with symptoms of suspected ovarian cancer in the UK (ROCkeTS): a multicentre, prospective diagnostic accuracy study

Article

作者: Keating, Patrick ; Manchanda, Ranjit ; Naskretski, Adam ; Gajjar, Ketankumar ; Kaushik, Sonali ; Selvi-Vikram, Radhika ; Sengupta, Partha ; Ramsay, Bruce ; Blake, Dominic ; Moshy, Roger ; Kwong, Fong Lien ; Timmerman, Dirk ; Rosello, Natalia ; Sharma, Aarti ; Roberts, Mark ; Palmer, Julia ; Hebblethwaite, Neil ; Baron, Sonali ; Hughes, Tracey ; Agarwal, Ridhi ; Exley, Kendra ; Menon, Usha ; Abdelbar, Ahmed ; Rick, Caroline ; Wood, Nicholas ; Scandrett, Katie ; Davenport, Clare ; Ottridge, Ryan ; Sturdy, Lauren ; Balogun, Moji ; Gentry-Maharaj, Alex ; Jermy, Karen ; Stobart, Hilary ; Sayasneh, Ahmad ; Harmer, Marianne ; Neal, Richard D ; Tarang, Majmudar ; Kehoe, Sean ; Gnanachandran, Chellappah ; Ames, Victoria ; Van Calster, Ben ; Russell, Michelle ; Kent, Robert ; Darwish, Ahmed ; Sundar, Sudha ; Abedin, Parveen ; Parker, Rob ; Macdonald, Robert ; Bourne, Tom ; Duncan, Tim ; Abdi, Shahram ; Vita, Lavanya ; Mallett, Sue ; Malhotra, Vivek ; Ciara, Mackenzie ; Johnson, Susanne ; Nagar, Hans ; Ghazal, Fateh ; Rai, Harinder ; Sinha, Anju ; Alawad, Hafez ; Deeks, Jon

BACKGROUNDMultiple risk-prediction models are used in clinical practice to triage patients as being at low risk or high risk of ovarian cancer. In the ROCkeTS study, we aimed to identify the best diagnostic test for ovarian cancer in symptomatic patients, through head-to-head comparisons of risk-prediction models, in a real-world setting. Here, we report the results for the postmenopausal cohort.METHODSIn this multicentre, prospective diagnostic accuracy study, we recruited newly presenting female patients aged 16-90 years with non-specific symptoms and raised CA125 or abnormal ultrasound results (or both) who had been referred via rapid access, elective clinics, or emergency presentations from 23 hospitals in the UK. Patients with normal CA125 and simple ovarian cysts of smaller than 5 cm in diameter, active non-ovarian malignancy, or previous ovarian malignancy, or those who were pregnant or declined a transvaginal scan, were ineligible. In this analysis, only postmenopausal participants were included. Participants completed a symptom questionnaire, gave a blood sample, and had transabdominal and transvaginal ultrasounds performed by International Ovarian Tumour Analysis consortium (IOTA)-certified sonographers. Index tests were Risk of Malignancy 1 (RMI1) at a threshold of 200, Risk of Malignancy Algorithm (ROMA) at multiple thresholds, IOTA Assessment of Different Neoplasias in the Adnexa (ADNEX) at thresholds of 3% and 10%, IOTA SRRisk model at thresholds of 3% and 10%, IOTA Simple Rules (malignant vs benign, or inconclusive), and CA125 at 35 IU/mL. In a post-hoc analysis, the Ovarian Adnexal and Reporting Data System (ORADS) at 10% was derived from IOTA ultrasound variables using established methods since ORADS was described after completion of recruitment. Index tests were conducted by study staff masked to the results of the reference standard. The comparator was RMI1 at the 250 threshold (the current UK National Health Service standard of care). The reference standard was surgical or biopsy tissue histology or cytology within 3 months, or a self-reported diagnosis of ovarian cancer at 12 month follow-up. The primary outcome was diagnostic accuracy at predicting primary invasive ovarian cancer versus benign or normal histology, assessed by analysing the sensitivity, specificity, C-index, area under receiver operating characteristic curve, positive and negative predictive values, and calibration plots in participants with conclusive reference standard results and available index test data. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN17160843).FINDINGSBetween July 13, 2015, and Nov 30, 2018, 1242 postmenopausal patients were recruited, of whom 215 (17%) had primary ovarian cancer. 166 participants had missing, inconclusive, or other reference standard results; therefore, data from a maximum of 1076 participants were used to assess the index tests for the primary outcome. Compared with RMI1 at 250 (sensitivity 82·9% [95% CI 76·7 to 88·0], specificity 87·4% [84·9 to 89·6]), IOTA ADNEX at 10% was more sensitive (difference of -13·9% [-20·2 to -7·6], p<0·0001) but less specific (difference of 28·5% [24·7 to 32·3], p<0·0001). ROMA at 29·9 had similar sensitivity (difference of -3·6% [-9·1 to 1·9], p=0·24) but lower specificity (difference of 5·2% [2·5 to 8·0], p=0·0001). RMI1 at 200 had similar sensitivity (difference of -2·1% [-4·7 to 0·5], p=0·13) but lower specificity (difference of 3·0% [1·7 to 4·3], p<0·0001). IOTA SRRisk model at 10% had similar sensitivity (difference of -4·3% [-11·0 to -2·3], p=0·23) but lower specificity (difference of 16·2% [12·6 to 19·8], p<0·0001). IOTA Simple Rules had similar sensitivity (difference of -1·6% [-9·3 to 6·2], p=0·82) and specificity (difference of -2·2% [-5·1 to 0·6], p=0·14). CA125 at 35 IU/mL had similar sensitivity (difference of -2·1% [-6·6 to 2·3], p=0·42) but higher specificity (difference of 6·7% [4·3 to 9·1], p<0·0001). In a post-hoc analysis, when compared with RMI1 at 250, ORADS achieved similar sensitivity (difference of -2·1%, 95% CI -8·6 to 4·3, p=0·60) and lower specificity (difference of 10·2%, 95% CI 6·8 to 13·6, p<0·0001).INTERPRETATIONIn view of its higher sensitivity than RMI1 at 250, despite some loss in specificity, we recommend that IOTA ADNEX at 10% should be considered as the new standard-of-care diagnostic in ovarian cancer for postmenopausal patients.FUNDINGUK National Institute of Heath Research.

2024-04-15·Clinical Cancer Research

Germline Mutations of Holliday Junction Resolvase Genes in Multiple Primary Malignancies Involving Lung Cancer Lead to PARP Inhibitor Sensitization

Article

作者: Chen, Yuping ; Yang, Jie ; Zhang, Jie ; Xie, Juntao ; Wang, Haoran ; Huang, Binhao ; Yuan, Jian ; Wang, Xinshu ; Wu, Jinhuan ; Yin, Hui

AbstractPurpose:The incidence of multiple primary malignancies (MPM) involving lung cancer has increased in recent decades. There is an urgent need to clarify the genetic profile of such patients and explore more efficacious therapy for them.Experimental Design:Peripheral blood samples from MPM involving patients with lung cancer were assessed by whole-exome sequencing (WES), and the identified variants were referenced for pathogenicity using the public available database. Pathway enrichment analysis of mutated genes was performed to identify the most relevant pathway. Next, the effects of mutations in relevant pathway on function and response to targeted drugs were verified by in vitro and in vivo experiments.Results:Germline exomes of 71 patients diagnosed with MPM involving lung cancer were sequenced. Pathway enrichment analysis shows that the homologous recombination repair (HRR) pathway has the strongest correlation. Moreover, HRR genes, especially key Holliday junction resolvases (HJR) genes (GEN1, BLM, SXL4, and RMI1), were most frequently mutated, unlike the status in the samples from patients with lung cancer only. Next, we identified a total of seven mutations in HJR genes led to homologous recombination DNA repair deficiency and rendered lung cancer cells sensitive to PARP inhibitor treatment, both in vitro and in vivo.Conclusions:This is the first study to map the profile of germline mutations in patients with MPM involving lung cancer. This study may shed light on early prevention and novel targeted therapies for MPM involving patients with lung cancer with HJR mutations.

2024-04-01·The Journal of Obstetrics and Gynecology of India

Comparison of Simple Ultrasound Rules by International Ovarian Tumor Analysis (IOTA) with RMI-1 and RMI-4 (Risk of Malignancy Index) in Preoperative Differentiation of Benign and Malignant Adnexal Masses

Article

作者: Dewangan, Shalinee ; Gupta, Sonal ; Chawla, Indu

BackgroundIOTA proposed Simple Ultrasound Rules in 2009 for preoperative diagnosis of ovarian masses based on ultrasound only. It is an accurate, simple and inexpensive method. RMI, however, requires CA125 level. While RMI-4 is the latest, RMI-1 is still the most widely used method. The present study was done to compare IOTA Rules with RMI-1 and RMI-4.PurposeTo differentiate benign and malignant adnexal masses preoperatively using IOTA simple rules and compare its accuracy with RMI-1 and RMI-4.MethodsA prospective observational study was performed from 1st November 2019 to 31st March 2021 in the Department of Obstetrics and Gynaecology, ABVIMS and Dr. RML Hospital, New Delhi. This study was conducted on 70 patients with adnexal masses who underwent pre-operative evaluation using IOTA Simple Rules, RMI-1 and RMI-4. Histopathology was used to compare the results.ResultsOut of 70 patients, 59 (84.3%) cases were benign and 11 (15.7%) were malignant. The IOTA Rules were applicable to 60 cases (85.7%), and the results were inconclusive in 10 cases (14.3%). Where applicable, the sensitivity and specificity of the IOTA Rules (88.9% and 94.1%, respectively) were significantly higher than RMI-1 (45.5% and 93.2%, respectively) and RMI-4 (45.5% and 89.8%, respectively). When inconclusive results were included as malignant, the sensitivity of the IOTA Rules increased (88.9% vs 90.9%); however, the specificity decreased (94.1% vs 81.4%).ConclusionIOTA Simple Rules were more accurate at diagnosing benign from malignant adnexal masses than RMI-1 and RMI-4. However, the rules were not applicable to 14% of the cases.