tbuckley/cabot-search huggingface dataset:
FGFR expression, fusion and mutation as detected by NGS sequencing of DNA and RNA.
Authors: Ivan De Dios, Wanlong Ma, Spiraggelos Antzoulatos, Jeffrey Estella, Maher Albitar
Journal: Journal of Clinical Oncology (2020)

e16061 Background: Fibroblast Growth Factor Receptors (FGFR 1-4 ) abnormalities (fusion, amplification and mutations) are common in urothelial, breast and endometrial cancers. However, FGFR 1-4 have been shown to play a major role in cell proliferation, differentiation, and apoptosis in other types of cancers including colorectal (CRC) and lung cancers. We explored the value of using DNA and RNA next generation sequencing (NGS) in determining the presence of abnormalities in FGFR 1-4 in various types of cancer. Methods: Using targeted panel and next generation sequencing (NGS), we analyzed DNA sequencing data (434 genes) in 438 Solid tumors and RNA data (1408 genes) in 160 lung cancers and 53 colorectal cancers (CRC). The expression levels of the CRC and lung cancer were also compared with expression levels of 32 cases of endometrial, urothelial and breast cancers as a group of cancers known to have high incidence. Results: The DNA data showed mutations in 85 samples and CNV in 12 samples. The detected mutations were 18% in FGFR1, 25% in FGFR2, 45% in FGFR3, and 12% in FGFR4. Only 20% of the detected mutations by NGS testing can be detected if the PCR-based FDA-approved kit was used. Analysis of the expression levels of FGFR 1-4 mRNA in CRC and lung cancer showed highest expression in FGFR2, followed by FGFR1 then FGFR3. Expression of FGFR4 was the lowest (P &lt; 0.0001). There was no difference between CRC and lung cancer in FGFR1 and FGFR2 mRNA, but FGFR3 was slightly higher in lung cancer as compared with CRC (P = 0.01). FGFR4 was significantly higher in CRC as compared with lung cancer (P &lt; 0.0001). No fusion involving FGFR 1-4 was detected in any of the tested CRC or lung cancers. Upon comparing overall expression between CRC/lung cancer with the group of cancers that are known to have high incidence of FGFR 1-4 abnormalities (urothelial, breast, and endometrial), FGFR1 and FGFR2 mRNA were significantly lower in CRC/lung cancers (P &lt; 0.0001 and P = 0.0002, respectively), but there was no significant difference in FGFR3. However, significant overlap is noted. In contrast, FGFR4 was significantly higher in CRC (P &lt; 0.0001). Conclusions: This data suggests that while FGFR 1-3 genes are overall expressed in CRC and lung, some cases may have significantly high expression of FGFR 1-3 and perhaps these cases should be singled out for treatment with FGFR inhibitors. Furthermore, NGS testing for mutations significantly more efficient and can detect significant number of mutations that can be missed if PCR-based testing is used. NGS testing of DNA and RNA is the most appropriate testing for abnormalities in FGFR 1-4 .
Risk score and prognostication modeling based on mRNA expressivity in the tumor microenvironment of hepatocellular carcinoma.
Authors: Sunyoung S. Lee, Yehia I. Mohamed, Sung Hwan Lee, Andrew Baird, Jillian Dolan, fateeha furqan, Ahmed Omar Kaseb
Journal: Journal of Clinical Oncology (2020)

e16658 Background: Stromal elements in the tumor microenvironment (TME) impact prognosis and response to therapy. Advances in mRNA-sequencing improved understanding of gene expressivity, but few models exist to model prognosis in association with mRNA expression. Methods: Clinical data and mRNA-seq of 256 patients (pts) with hepatocellular carcinoma (HCC) were obtained from TCGA. The expressivity of 191 genes enriched in cellular and structural components of the TME and clinical data were analyzed using machine learning, multivariable COX model, and Kaplan-Meier (KM) analysis to model risk score (RS) for prediction of prognosis. Results: Prognostication was modeled with higher risk score (RS) representing worse prognosis. Gene expression associated with poor (P) and good (G) in stage 1 and 2 HCC was identified (refer to presentation). RS (stage 1) = 5.997 - 0.589 × (Age at diagnosis −7.979E-06 ) - 4.818 × (P/G −0.009 ); RS (stage 2) = -5.704 - 0.780 × (Age at diagnosis −9.383E-06 ) + 7.228 × (P/G −0.004 ). Based on RS, pts were clustered into 2 groups in each stage - high and low RS groups, showing two KM curves with P &lt; 0.05, HR = 3.213 (95% CI 2.212 – 4.347) in stage 1; HR = 2.733 (95% CI 2.131 – 3.426) in stage 2, confirming the validity of RS modeling. Analysis of immune profiles in high and low RS groups shows that expression of genes associated with immunosuppressive factors, desmoplastic reaction, neutrophils, and co-inhibitory factors of T-cells are higher in high RS group in both stages (p &lt; 0.05). Conclusions: Machine learning-assisted mathematical modeling of RS and gene analysis identified TME-related genes and gene groups that are strongly associated with worse prognosis in stage 1 and 2 of HCC. RS could potentially prognosticate pts in the clinic with available genomic profiles.
儿童原发性肺结核82例误诊原因分析
Authors: 雷鸣, 曾鸿雁, 余奕
Journal: BMJ (2005)

原发性肺结核为肺结核类型之一,多见于儿童.早期因临床症状及X线表现不典型,易误诊.咸宁市结核病防治所从1995至2004年共收治儿童原发性肺结核123例,现就其中入院前被误诊的82例分析如下。
Comparison of intraoperative imprint cytology with frozen section for lymph node metastasis in patients with head and neck cancer.
Authors: Saheer Neduvanchery
Journal: Journal of Clinical Oncology (2020)

e18548 Background: Intraoperative evaluation of lymph nodal metastasis in head and neck carcinoma assumes importance in deciding the extent of lymph node dissection. Frozen section is the most commonly employed technique. But it requires significant investment in terms of resources, time and personnel. Intraoperative imprint cytology is a rapid, reliable and an inexpensive alternative. So we conducted a prospective diagnostic test accuracy study to assess the diagnostic accuracy of intraoperative imprint cytology and frozen section for lymph node metastasis in Head and neck Cancer when compared to Gold standard, which is the final Histopathology. Methods: All patients presenting with squamous cell carcinoma of head and neck with clinically N0 neck undergoing surgery as primary treatment were included in the study. For patients undergoing surgery, neck nodal tissue were sent for intraoperative assessment of clinically suspicious nodes. Intraoperative assessment was done by imprint cytology and frozen section and was reviewed and reported by two independent pathologist. The sensitivity, specificity and accuracy of imprint cytology and frozen section were calculated with reference to the final histopathology report. Time duration for reporting were also calcuted for both. Results: Total 34 patients with clinically N0 neck were included in the study and 85 slides were examined for frozen section and imprint cytology. Occult nodal metastasis was found in 16 patients (47.06%). The mean time duration for reporting for frozen was 41.18 ±3.62 minutes where as for imprint cytology it was 18.12 ±2.01 minutes. The concordance rate between the frozen section and imprint cytology was 94.12%. The sensitivity of frozen section was 100 % where as for imprint cytology it was 85.7 %( p = 0.00). The specificity was 98.6 % for frozen section and 95.8 % for imprint cytology (p = 0. 27). The positive predictive value was 93.3 % and 80 % for frozen section and imprint cytology respectively (p = 0.01). The negative predictive value was 100% for frozen section and 97.1% for imprint cytology (p = 0.12). The accuracy for frozen section was 98.8 % where as for imprint cytology it was 94.1%(p = 0.09). Conclusions: Imprint cytology provides a cheaper, accurate, reliable and a rapid alternative for frozen section for intraoperative assessment of neck nodes in squamous cell carcinoma of head and neck and it assumes importance in resource driven countries like India.
重视子宫颈癌前病变的规范化诊治
Authors: 李楠, 章文华
Journal: BMJ (2009)

近年,宫颈癌前病变--宫颈上皮内瘤变(CIN)的患病人数显著增加.美国每年新诊断病例为1 500 000例,患病率为2.7%[J].我国山西省宫颈癌高发区CIN检出率为8.2%～10.6%[2-3].我院(2003年)统计,近5年住院治疗的CIN病例数为前15年之和的6.4倍[4].因此,各级妇科医生都应高度重视宫颈癌前病变的规范化诊治。
Salvage radiotherapy after chemotherapy for unresectable locally advanced non-small cell lung cancer in real world.
Authors: Qinghua Xu, Min Hu, Xiaoshuai Yuan, Fangjuan Li, Hui Liu, Yaping Xu
Journal: Journal of Clinical Oncology (2020)

e21052 Background: For patients with unresectable stage III disease, combined modality therapy (chemoradiation) is superior to radiation alone, and concurrent chemoradiotherapy (CCRT) is superior to sequential chemoradiotherapy (SCRT). The current standard of care for unresectable stage III disease is CCRT. Consequently, CCRT is commonly given to patients with minimal or no comorbidities, a good general condition, and who are relatively young. SCRT may be a valuable alternative for patients who are not eligible for CCRT. However, the role of salvage radiotherapy (SRT) after chemotherapy for patients with unresectable stage III disease without CCRT or SCRT is currently unknown. Methods: Patients with unresectable stage III disease receiving chemoradiotherapy were enrolled. All patients were treated with CCRT, SCRT or SRT. Overall survival (OS) was estimated by Kaplan-Meier curves. Results: From May 2014 to September 2018, 216 patients were enrolled, including 65 (30.1%) who received CCRT, 80 (37.0%) who received SCRT, and 71 (32.9%) who received SRT. No significant difference in gender, age, performance status, TNM stage, or EGFR gene status among the three groups. The median OS for the entire cohort was 22.1 (range: 18.4–25.8) months. The median OS in CCRT, SCRT, and SRT group were 29.7, 21.3, and 19.1 months, respectively (P = 0.011). The difference was statistically significant between CCRT group and SCRT or SRT group but was not between SCRT and SRT group. The 1-year survival rate in CCRT, SCRT, and SRT group were 89.2%, 75.0%, and 75.2%, respectively. However, the 3-year survival rate in CCRT, SCRT, and SRT group were 42.7%, 32.7%, and 9.6%, respectively. However, CCRT also has a higher rate of Grade 3 or 4 acute esophagitis and pneumonitis . Conclusions: The current study demonstrated compared with CCRT and SCRT, SRT had reduced patient survival survival time significantly.
Evidence-based deep vein thrombosis therapy in China: call for more studies
Authors: 吴庆华
Journal: BMJ (2008)

静脉血栓栓塞症(venous thromboembolism,VTE)是一种发病率高,严重危害人类生命和健康的常见血管疾病,在发展中国家大约每年有3～6千万人患病.美国单纯深静脉血栓形成(deep venous thrombosis,DVT)年发生率145/10万,肺栓塞的发病率高达69/10万,因DVT引起肺栓塞而死亡的人数每年约20万,住院患者中的肺栓塞发生率比一般人群高10倍.DVT形成是一种可危及生命的常见疾病.目前国内对静脉血栓栓塞症越来越重视,如国家十五科技攻关项目就针对肺血栓栓塞症的规范化诊治开展研究。
Multistate Markov modelling of long-term outcomes in immunotherapy for metastatic renal cell carcinoma (mRCC) using machine-learned dynamic Bayesian networks.
Authors: Alind Gupta, Darren Brenner, Paul Arora
Journal: Journal of Clinical Oncology (2020)

e14049 Background: Patient-level heterogeneity in response to treatment remains a major challenge in cancer immunotherapy. Long-term individual-level modelling of survival, tumour response and safety outcomes jointly can help improve efficacy and durable clinical benefits. Machine-learned Bayesian networks provide a solution to the “black box” problem of other machine-learning approaches. Objectives: To develop a dynamic Bayesian network model for multivariate risk prediction, survival modelling and long-term simulations of immunotherapy patients using a simulated trial dataset. Methods: A simulated randomized clinical trial dataset for second line immunotherapy of patients with renal cell carcinoma was used for analysis. We machine-learned a dynamic Bayesian network from censored data with incorporation of prior clinical knowledge. Classification performance, probability calibration, goodness-of-fit metrics and prognostic variables were calculated following TRIPOD guidelines. Results: The machine-learned graphical model encoded expected relationships between variables with minimal prior information. Visual and numerical goodness-of-fit checks for survival extrapolations showed that the model fitted data well and was appropriate. Probability calibration was &lt; 10% from ideal. Classification performance for overall survival was high ( c-statistic ~0.85) soon after treatment initiation and gradually plateaued over time. Prognostic variables were calculated by treatment arm for overall survival and severe adverse events. Conclusions: Dynamic Bayesian network model was useful for transparently representing joint relationships between all variables in the trial dataset, for multivariate risk prediction and long-term extrapolations that can be used in economic evaluations for health technology assessments in oncology.
Differences in real-world liver cancer treatment patterns among people living with HIV/AIDS (PLWHA) compared to those without HIV/AIDS (PWoHA).
Authors: Angelica Falkenstein, Andrew J. Klink, Ajeet Gajra
Journal: Journal of Clinical Oncology (2020)

e19010 Background: Antiretroviral therapy (ART) has brought life expectancy among PLWHA on par with PWoHA, but the disparity in cancer incidence and mortality among PLWHA remains high. Hepatocellular carcinoma (HCC) is 4 times more common in PLWHA and an important cause of mortality. Guidelines now support treatment and management of cancer among PLWHA to follow those for PWoHA, but PLWHA have been excluded from registrational trials of novel agents. This study aimed to assess real-word differences in demographics and systemic therapy patterns for HCC among PLWHA and PWoHA. Methods: Adult patients with ≥2 claims for HCC between 1/1/13-12/31/18 (earliest claim = index date), ≥3 months data pre/post index date, and no evidence of clinical trial participation, pregnancy or other malignancy prior to index date were identified from Symphony Health longitudinal prescription and medical claims. Patient characteristics and treatment patterns were summarized by descriptive statistics, and comparisons across HIV status were made on univariate analyses. Times to discontinuation were estimated by Kaplan-Meier method and compared by log-rank tests. Results: There were 9,904 HCC PWoHA who received systemic therapy. Of 862 PLWHA with HCC, 162 (19%) received systemic therapy. PLWHA differed significantly from PwoHA: median age at diagnosis (60 v 63 years), male preponderance (84% v 71%), geography (Northeast, 41% v 19%; West, 22% v 45%), Charlson Comorbidity Score (median 7 v 1), depression (11% v 6%), chronic pulmonary disease (20% v 12%), liver disease (66% v 52%) and kidney disease (17% v 7%, all P&lt; 0.05), respectively. First line (1L) therapy differed among PLWHA and PWoHA: sorafenib (34% v 25%), everolimus (1% v 4%), and doxorubicin-based regimens (42% v 33%; all P&lt; 0.05). IOs were used in 1L and 2L among 584 (6%) and 223 (15%) of PWoHA and among 8 (5%) and 6 (19%) PLWHA, respectively (all P&gt; 0.05). Median times from 1L start to 2L were numerically shorter among PLWHA and PWoHA (4.7 v 5.5 months; P= 0.77). The minority of patients among PLWHA and PWoHA continued onto 2L (20% and 15%, P&gt; 0.05) and 3L (7% and 3%, P&lt; 0.01), respectively. Conclusions: HCC is diagnosed at younger age among PLWHA v PWoHA. Important differences in comorbid disease burden in addition to HIV can impact clinical decision making in PLWHA. Future real-world research is needed to understand disparities in outcomes of PLWHA and develop guidelines specific to this group.
早期无创正压通气救治重症甲型H1N1流行性感冒一例
Authors: 谢德荣, 张华峻, 杜黎明
Journal: BMJ (2010)

患者男,50岁.2009年11月24日,因咳嗽4 d伴发热、痰中带血1 d就诊.患者既往体健.入院前4 d因受凉出现咳嗽、无痰、全身酸痛、乏力,当地社区服务中心给予头孢他啶治疗,症状无减轻,并出现胸闷、活动后气促、畏冷、发热,体温最高达39.1 ℃,伴有痰中带血,门诊以发热原因待查收入院.体检:体温39.1 ℃,血压150/90mmHg(1 mm Hg=0.133 kPa),脉搏124次/min,呼吸32次/min,神志清楚,口唇紫绀,半卧位,双中下肺可闻及湿啰音.实验室检查白细胞5.29×109/L,分类淋巴细胞0.11,中性粒细胞0.86,钾2.86 mmol/L,ALT 68 U/L,AST59 U/L,肌酸激酶535 U/L,乳酸脱氢酶453 U/L。
Comprehensive next-generation sequencing to portray distinctive molecular characteristics of hypermutant lung cancer.
Authors: Hongbin Zhang, Yuan Wang, Qiaoxia Ji, Hongmei Cai, Xiangcun Liang, Jiong Xie, Hua Li, Jun Wang, Guiyun Zhu, Erpeng Tian, Lingling Zhu, Lingzhi Cui, Wenzhong Su, Mingming Yuan, Rongrong Chen, Min Zhao
Journal: Journal of Clinical Oncology (2020)

e15255 Background: Tumor mutation burden (TMB) has been confirmed to predict the sensitivity to immunotherapy across multiple tumor types. Multiple genetic factors have been confirmed to increase the level of TMB, such as mutations in DNA damage repair (DDR) genes, POLE/POLD1, and high microsatellite instability (MSI). However, the extent that these factors contribute to hypermutation in lung cancer has not been fully investigated. Methods: We retrospectively reviewed the genetic profiles of 1000 lung cancer patients (pts) who underwent 1021-panel matched tumor-normal next-generation sequencing using tumor tissue samples and peripheral blood. Their TMB status were analyzed to determine the threshold of hypermutation. The clinicopathological characteristics, genetic profiles and genetic factors related to hypermutation were investigated for the pts in hypermutant cohort. Results: The threshold of hypermutation was determined as 19 muts/MB (top 5% in 1000 pts). As a result, 53 pts were included in the hypermutant cohort. A total of 1725 nonsynonymous somatic variants in 506 genes were identified. The most frequently mutated genes included TP53 (88.7%), LRP1B (71.7%), MLL2 (35.8%), EPHA5 (34.0%), and FAT1 (34.0%). KRAS was mutated in 17% pts, whereas mutations in EGFR, BRAF, ERBB2, MET were identified less commonly. MSI-high was observed in 5 cases. A germline mutation in BRCA1 gene was identified in an adenocarcinoma patient. Compared to genetic profiles of non-small cell lung cancer from TCGA database, mutations in multiple DDR genes were enriched in the hypermutant cohort (Table). No known driver mutation in POLE/POLD1 was identified. Conclusions: MSI-high and mutations in DDR genes may be associated with high level of TMB, whereas POLE/POLD1 driver mutations may not be related to hypermutant lung cancer. Hypermutant lung cancer displays distinctive molecular features that may be used as complementary indicators to screening pts sensitive to immunotherapy. [Table: see text]
Cardiovascular risk factors in hypertensives complicated with non-alcoholic fatty liver but normal aminotransferase
Authors: Jian-feng Jia, Yu-sa Lu
Journal: BMJ (2011)

Objective To explore cardiovascular risk factors in patients of hypertension (HTN) complicated with non-alcoholic fatty liver but normal aminotransferase. Methods Forty-four cases (control group) of uncomplicated hypertension and 56 cases (study group) of hypertension complicated with nonalcoholic fatty liver but normal aminotransferase were screened from those who visited physical examination center of the hospital for regular checks-up during October 2009 to June 2010. Blood pressure ( BP), body mass index ( BMI), fasting plasma glucose (FPG), total serum cholesterol (TC) , triglyceride (TG), highdensity lipoprotein-cholesterol ( HDL-C ), low-density lipoprotein-cholesterol ( LDL-C ), gammaglutamyltransferase ( GGT ), uric acid ( UA ) , highly-sensitive C-reactive protein ( hs-CRP) and homocysteine (Hey) of the two groups were compared. Results Comparing with the control group, the study group had higher diastolic blood pressure ( DBP) (t = 1898. 5, P < 0. 05) , BMI (t = - 5. 036, P < 0.01), FPG (t= -2.026, P<0.05), TG (t = 1923. 5, P<0.05), GGT (t = 1789, P <0.01), UA 0 = 1715, P<0.01), hs-CRP (t = 1832.5, P < 0.01) and lower level of HDL-C (t =2357.0, P< 0. 01). Serum activity of GGT correlated positively with BMI (rs = 0. 349, P = 0. 000), TG ( rs = 0.413,P =0.000), UA (rs =0.446, P= 0.000) and hs-CRP (rs =0.350, P = 0.000), respectively.Conclusions When patients of hypertension complicated with non-alcoholic fatty liver but normal aminotransferase, their cardiovascular risk factors clustered further, with serum activity of GGT obviously increased which correlated positively with various risk factors, indicating increase in cardiovascular risks. 

Key words: 
Hypertension;  Fatty liver, non-alcoholic;  Gamma-glutamyltransferase
男人也有情绪问题
Authors: 曾昭耆
Journal: BMJ (2004)

61岁男性,工人,2个月来频发胸闷憋气,位于胸骨后及左胸部,夜间发作较多,可达3～4次,伴出汗,均可因服用硝酸异山梨酯(消心痛)而缓解,日间很少发病.曾多次夜间急诊,心电图均正常.一次发作后即刻到外院就诊,急诊医生认为症状典型,拟收入院做冠状动脉造影和介入治疗.但在留院观察期间,几次发作时复查心电图及心肌酶均正常,故给予单硝酸异山梨酯(鲁南欣康)及阿司匹林等药后回家,其后发作仍同以往.今日来我院门诊,查体:血压125/80 mm Hg(16.6/10.6 kPa),心率72次/min,律齐,无杂音,心电图正常.但患者情绪凝重、压抑,遂问之:有何忧愁事?患者不语,但眼圈发红,似有难言之事.将诊室门关闭,即见患者流泪,再问:可否告诉我?
Management of heart failure patients with <scp>COVID</scp>‐19: a joint position paper of the Chinese Heart Failure Association &amp; National Heart Failure Committee and the Heart Failure Association of the European Society of Cardiology
Authors: Yuhui Zhang, Andrew J.S. Coats, Zhe Zheng, Marianna Adamo, Giuseppe Ambrosio, Stefan D. Anker, Javed Butler, Dingli Xu, Jingyuan Mao, Muhammad Shahzeb Khan, Ling Bai, Alexandre Mebazaa, Piotr Ponikowski, Qizhu Tang, Frank Ruschitzka, Petar Seferovic, Carsten Tschöpe, Shuyang Zhang, Chuanyu Gao, Shenghua Zhou, Michele Senni, Jian Zhang, Marco Metra
Journal: European Journal of Heart Failure (2020)
Genomic alterations associated with the progression from castration-sensitive to castration-resistant metastatic prostate cancer based on machine learning analysis of cell-free DNA genomic profile.
Authors: Edwin Lin, Andrew W. Hahn, Roberto Nussenzveig, Sergiusz Wesolowski, Benjamin Louis Maughan, Taylor Ryan McFarland, Nityam Rathi, A. Oliver Sartor, Guru Sonpavde, Umang Swami, Manish Kohli, Thereasa A. Rich, Mark Yandell, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2020)

e17596 Background: Metastatic castration-sensitive prostate cancer (mCSPC) eventually progresses to metastatic castration-resistant prostate cancer (mCRPC), which has few treatment options and carries a poor prognosis. We hypothesize that there are specific genomic alterations (GAs) associated with the progression from mCSPC to mCRPC. Methods: Patients (Pts) with mCSPC and mCRPC undergoing next-generation sequencing of cell-free DNA by a CLIA certified lab (G360, Guardant Health Inc., Redwood City, CA) as a part of routine care were retrospectively identified. Principal components analysis, an unsupervised ML algorithm, was used for data exploration and visualization. A combination of feature selection and supervised machine learning classification algorithms were used to identify genes associated with mCRPC. Gene Ontology enrichment analysis was used to identify pathways enriched for mCRPC-associated GAs. Patterns of mCRPC-associated GAs at a gene- and pathway-level were identified by Bayesian networks fitted using an exact structure learning algorithm. Results: 154 Pts with mCSPC and 187 Pts with mCRPC were included. A set of 16 GAs that robustly distinguished mCRPC from mCSPC (PPV = 94%, specificity = 91%) using supervised machine learning algorithms. These GAs, primarily amplifications, corresponded to AR, MAPK signaling, PI3K signaling, G1/S cell cycle, and receptor tyrosine kinases (RTKs). Positive statistical dependencies were observed between genes in these pathways. At a pathway-level, the presence of G1/S GAs in mCRPC samples increased the likelihood of harboring GAs in RTK, MAPK, and PI3K signaling. Limitations: The retrospective nature of our study means that unknown exposures could act as confounding variables, however this is representative of real-world clinical settings. Although the strength of this study is inclusion of clinically annotated patient samples, the limitation is that patients with mCSPC and mCRPC were unmatched. Conclusions: These results provide evidence that progression from mCSPC to mCRPC is associated with stereotyped concomitant gain-of-function in the RTK, PI3K, MAPK, and G1/S pathways in addition to AR. Upon external validation, these hypothesis generating data may warrant further investigation into combinatorial therapies that target these pathways.