Genomic Profiling of Chinese Urothelial Carcinoma Patients

doi:10.21203/rs.3.rs-44817/v1

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Genomic Profiling of Chinese Urothelial Carcinoma Patients

https://doi.org/10.21203/rs.3.rs-44817/v1

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published 15 Feb, 2021

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Background

Urothelial carcinoma (UC) is the most common genitourinary malignancy in China. In this study, we studied the genomic features in Chinese UC patients, and investigated the concordance of genetic alterations between serum circulating tumor free DNA (ctDNA) and matched tumor tissue.

Methods

A total of 112 UC patients were enrolled, and 31 of which were upper tract UC (UTUC) and 81 were UC of bladder (UCB), respectively. Utilizing target next-generation sequencing, we analyzed genomic alterations of 92 selected genes.

Results

94.64%, 86.61% and 62.50% of patients in our cohort were identified as having valid, oncogenic or actionable somatic alterations, respectively, and the most altered genes were TP53, KMT2D, KDM6A, FAT4, FAT1, CREBBP and ARID1A. HRAS (22.0% vs 3.7%) and KMT2D (59.26% vs 34.57%) were more altered in UTUC than in UCB in our cohort. Comparisons of somatic alterations of UCB and UTUC between our cohort and western cohorts revealed significant differences in gene prevalence. Notably, 28.57%, 17.86% and 47.32% of cases harbored alterations in FGFRs, ERBBs and DNA damage repair genes, respectively. Furthermore, 75% of patients carried non-benign germline variants, but only two (1.79%) were pathogenic. By comparison of ctDNA and matched tumor tissue, the overall concordance for genomic alterations was 42.97% (0-100%). 47.25% of alterations detected in ctDNA were not detected in the matched tissue, and 25.58% of which were oncogenic.

Conclusions

We found a unique genomic feature of Chinese UC patients. A good concordance of genomic features between ctDNA and tissue samples were identified.

Cancer Biology

Oncology

Urothelial carcinoma

Genomic alterations

ctDNA

Urothelial carcinoma (UC) is the most common genitourinary malignancy in the world [1]. As reported by the national cancer center of China, the estimated number of newly-diagnosed and mortality of urothelial carcinoma patients in 2015 was 80,500 and 32,900, respectively [2]. Most non-muscle invasive bladder cancer patients will have disease recurrence and progression to the invasive or metastatic disease within 5 years [3]. Treatments for locally advanced or metastatic disease have been dramatically changed in the last three years, especially with the development and approval of the five immune checkpoint inhibitors (ICIs) and one FGFR inhibitor by the U.S. Food and Drug Administration (FDA).

Previous studies have widely characterized the genomic features of urothelial carcinoma, but the samples were mainly limited to the Caucasians [4]. To date, rare research had studied the molecular features of Chinese UC patients. The genomic alterations between western and Chinese UC patients may differ, especially considering the exposure of aristolochic acid and the different genetic backgrounds [5]. Meanwhile, as most of the genomic research in UC conducted on the tumor tissue samples, patients without sufficient and valid achieved tumor samples or unable to biopsy will miss the chance of target therapies. Recently, circulating cell-free tumor DNA (ctDNA) has been widely studied and applied in cancer diagnosis, treatment selection and monitoring, especially for lung cancer. For localized bladder cancer, ctDNA in plasma and urine was proved to be detectable even at the early phase of disease and associated with disease recurrence or progression [6]. However, whether ctDNA in blood or urine would be an effective substitution for tissue for genetic testing in UC is still unknown.

In the present study, we analyzed the germline and somatic gene alterations in 112 Chinese UC patients. The basic genomic alteration profiles were described and compared with corresponding Western data. Meanwhile, we compared the concordance of genetic alterations between ctDNA in plasma and matched tumor tissue to comprehend the utility of liquid biopsy samples in UC patients.

Samples source and ethic data

In total, formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood in EDTA (for germline tests) from 112 diagnosed UC patients (Supplemental Table 1) were collected with the signing of informed consent and agreements to publish the results for research purpose. All tumor tissues were pathologically reviewed to contain at least 20% tumor cells. 34 patients who cannot provide sufficient or valid tumor tissue samples were collected blood for ctDNA testing instead. Among enrolled patients, 20 of them agreed to provide additional blood samples for comparison of the genomic differences between blood and matched tumor.

Dna Isolation

The FFPE tissues and peripheral blood mononuclear cells were collected to extract DNA using DNeasy Blood & Tissue Kit (Qiagen, Inc.) under the manufacturer’s instructions. Cell-free DNA (cfDNA) was extracted from serum using the QIAamp Circulating Nucleic Acid Kit (Qiagen, Inc.) following the protocol of the manufacturer. The purified gDNA and cfDNA were quantified using the Qubit 3.0 Fluorometer (Life Technologies, Inc.) and StepOnePlus System (Life Technologies, Inc.).

Target Next-generation Sequencing

For the matched germline and tumor samples, 100 ng of DNA was sheared with a Covaris E210 system (Covaris, Inc.) to get 200 bp fragments. We performed next generation sequencing of tumor and gDNA matched germline DNA using Accel-NGS 2S DNA Library Kit (Swift Biosciences, Inc.) for library preparation and xGen Lockdown Probes kit (IDT, Inc.). The custom xGen Lockdown probe was synthesized by IDT, Inc. for the exons and selected intronic regions of 92 genes (Supplemental Table 2). The prepared library was quantified using the Qubit 3.0 Fluorometer (Life Technologies, Inc.), and quality and fragment size were measured using Agilent 2100 Bioanalyzer (Agilent Technologies, Inc.). Samples underwent paired-end sequencing on an Illumina Nextseq CN500 platform (Illumina Inc) with a 150-bp read length. Mean coverage of 1260.5×, 3759.3 × and 223.6 × were achieved for tumor gDNA, blood cfDNA and peripheral blood mononuclear cells gDNA, respectively.

Data Processing

Raw sequencing data were aligned to the reference human genome (UCSC hg19) by Burrows-Wheeler Aligner. After removing duplicate and local realignment, we applied Genome Analysis Toolkit (GATK) for single nucleotide variation (SNV), insertion and deletion (inDel) calling. Next, after removing the germline alterations from matched blood samples, the somatic alterations were obtained. Variants were annotated using the ANNOVAR software tool. Copy number was analyzed using CNVkit. Genomic alterations data from The Cancer Genome Atlas database (TCGA) and Memorial-Sloan Kettering Cancer Center (MSKCC) was downloaded from cBioPortal (http://www.cbioportal.org).

Statistical analysis

Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) statistical package and Graphpad (Prizm 8). Differences were considered significant if p < 0.05.

Demographic and clinical data

The demographic and clinical data of patients enrolled in our cohort were summarized in Table 1. Of the enrolled patients, 72.32% were bladder cancer (81/112), and the rest were diagnosed as upper tract UC (27.68%, 31/112), including carcinoma of the renal pelvis and ureteral. The median age at diagnosed was 67 (range 25–86). The sex ratio between males and females was 2.61:1, which was close to the sex ratio (2.97:1) in Chinese UC patients reported by the national cancer center of China. The amounts of enrolled smoker and non-smoker were the same (56 versus 56).

Somatic Alterations In Chinese Uc Patients

In total, 106 of 112 samples (94.64%) had been identified with valid somatic alterations. The mean and median counts of somatic alterations per sample were 6.05 and 4, respectively. Six samples were negative for somatic mutations identification after excluding the germline alterations. The most frequently mutated genes in our cohort were TP53 (48%), KMT2D (43%), KDM6A (23%), FAT4 (21%), CREBBP (20%), ARID1A (19%) and FAT1 (18%), respectively (Fig. 1A). Notably, 62.50% (70/112) and 86.61% (97/112) patients in our cohort were identified as having actionable and oncogenic alterations according to the OncoKB database, respectively [7]. No significant difference was found in gene prevalence between low- and high-grade urothelial carcinoma. Pathway analysis indicated that the most frequently enriched pathways were Chromatin regulatory (73.21%), RTK-RAS-MAPK (62.50%), cell cycle (53.57%), DNA damage repair (DDR, 47.32%), PI3K-mTOR (33.93%) and Wnt (32.14%), respectively (Fig. 1B). We didn’t find any significant genomic difference between high- and low-grade UC patients.

Germline Alteration

Excluded of variants identified as benign or likely benign according to the American College of Medical Genetics and Genomics (ACMG) guideline, 75.89% (85/112) patients in our cohort harbored at least one germline alteration (Supplemental Table 3). After exclusion of known and likely benign variants, 244 germline variants were identified. However, only two patients (1.85%) had variants that could be identified as pathogenic or likely pathogenic, including a ERCC4-p. Lys481fs and a BRCA2- p.Thr3030fs (Supplemental Table 3). The patient harbored deleterious BRCA2 germline variants was also concurrent with prostate cancer. None pathogenic or likely pathogenic germline variant associated with Lynch syndrome, including MLH1, MSH2, MSH6 and PMS2 genes, was identified in UTUC and UC patients of our cohort.

Differences of somatic gene alterations in UC patients between our cohort and Western cohort

To determine the potential difference of genomic features between Western and Chinese UC patients, we compared the alterations data of the selected 92 genes between our cohort and Western cohorts (UC data published by TCGA and UTUC data published by MSKCC). The prevalence of alterations in FGFR4, KDM5C, TERT, PDGFRB, FLT3, FLCN, MSH6, FLT1 were higher in UCB patients in our cohort, compared with TCGA (Fig. 2A). As for UTUC, a higher mutated frequency of multiple genes, including TP53, LRP1B, KMT2D, FAT4, BRCA1, FGFR2 and BRIPI, were found in our cohort (Fig. 2B). On the contrary, the mutation frequency of FGFR3 gene in the MSKCC cohort was three times higher than that in our cohort (48.24% versus 16.13%, p < 0.001).

Differences Of Somatic Gene Alterations Between Utuc And Ucb

To elucidate the differences of somatic gene alterations between UTUC and UCB, we compared the alterations from 81 UCB samples and 31 UTUC samples in our cohort. The genomic features of UCB and UTUC were similar, while KMT2D (34.57% vs 64.52%, p < 0.01), HRAS (3.7% vs 19.35%, p < 0.01) and CDKN2A (2.47% vs 12.9%, p < 0.05) were more mutated in UTUC than in UCB (Fig. 2C). A higher mutated frequency of HRAS was also presented in UTUC compared with UCB in Western cohorts, but with additionally significantly different prevalence in FGFR3, TP53, TERT, RB1, LRP1B, FAT4, KMT2A, ARID1A, BRIP1, TSC1 genes (Fig. 2D).

Genomic Alterations In Fgfr Genes

28.57% (32/112) patients had at least one somatic alteration in FGFR genes (including FGFR1, FGFR2, FGFR3 and FGFR4), but only 11 patients’ alternations could be defined as gain of function (Fig. 3A). Notably, six of these patients had multiple oncogenic alterations in FGFR genes. Same to previous studies’ results, the most altered gene was FGFR3 (13.39%). Hotspot variants, including FGFR3-p.Ser249Cys, p.Arg248Cys and p.Tyr373Cys were identified in six samples, while FGFR3-TACC3 fusion was only identified in two patients. Three novel variants (defined as unreported in any other research or single nucleotide polymorphism database before and without ExAC frequency), including p.His349Asn, p.Val166Met and p.Thr755Lys of FGFR3 were identified, though the functions were still unknown (Fig. 3B). Nine patients (8.04%) were identified with FGFR2 alterations, of which only three alterations could be defined oncogenic, including one p.Asn549Lys, one p.Lys659Met and one copy number gain (copy number 32.87). No FGFR2 fusion was identified. Four novel variants with unknown function, including p.Gly305Arg, p.Tyr207Phe, p.Met803Leu and p.Gln683Ter of FGFR2 gene were identified in this study. Only six patients carried FGFR1 gene alterations, and half of them were amplification. Eight patients (all were bladder cancer) carried nonsynonymous single nucleotide variants with unknown function in FGFR4 gene.

Genomic Alterations In Erbb Family

20 of our cases (17.86%) carried somatic alterations in the ERBB genes (EGFR, ERBB2 and ERBB3), and three of them had dual alterations (Fig. 3C). Five patients (4.46%) carried EGFR gene alteration and two of them had EGFR copy number gain. Notably, one patient had an activated EGFR exon 20 insertion (EGFR-p.Val769_Asp770insAspAsnPro) and copy number gain. We observed ERBB2 alterations in 12 patients (10.71%) s, and most of the oncogenic alterations located in furin-like cysteine rich region (amino acid 190–343) and protein tyrosine kinase domain (amino acid 721–975) (Fig. 3D). Two of the five identified ERBB3 alterations were in the furin-like cysteine rich region (amino acid 182–332) and oncogenic.

Somatic Alterations In Dna Repair Pathway

We observed 47.32% of cases had alterations in the DDR pathway as defined by the MSKCC DDR gene panel [8], including 37 (45.68%, 37/81) UCB patients and 16 (51.61%,16/31) UTUC patients, respectively. Distribution of alterations among specific DDR pathway was similar, with slight enrichment in Fanconi anemia (FA) pathway (Fig. 4A). The most frequently mutated DDR genes were BRCA2 (10.71%), ATM (9.82%), ERCC2 (8.93%), BRCA1 (7.14%) and BRIP1 (6.25%), respectively (Fig. 4B). Among patients carried DDR gene alterations, only 16 of them (14.29%) had at least one known or likely deleterious somatic DDR alterations (Fig. 4C). The distribution of specific genes was exhibited in Fig. 5C, and the most frequently mutated DDR genes with known or likely deleterious variants were ATM (n = 7, 31.82%) and BRCA2 (n = 5, 22.73%). Eighteen patients (16.07%) carried somatic alterations in DNA mismatch repair (MMR) genes, including in MLH1, MSH2, MSH6 and PMS2. The majority of these MMR gene alterations were unknown of function, with four exceptions of alterations in MSH2 and MLH1, which could be defined as loss of function.

Concordance of genetic alterations between ctDNA in serum and matched tumor tissue

Twenty matched tumor tissue and blood samples were collected to comprehend the concordance and discordance of genomic alterations between different sample types in UC. Only three patients’ matched samples were collected with an interval time over one month (7 months for P074, 18 months for P084 and 34 months for P110, respectively). In total, 99 and 91 somatic alterations were identified in tumor and serum ctDNA samples from 20 patients who underwent genomic testing for matched tumor tissue and serum ctDNA samples, respectively. Only one patient’s ctDNA was negative for valid somatic alterations identification, while matched tumor samples were positive for alterations calling. Conversely, in Patient 20, ctDNA analysis revealed oncogenic mutations in PIK3CA, TP53, ARID1A and KDM6A with allele fractions all beyond 3%, for which there was no corresponding valid alteration in the matched tissue sample (Fig. 5A). There was no significant difference between tissue and blood in the median number of genomic alterations (4 versus 4). By comparison of blood and matched tumor tissue, the overall concordance for genomic alterations and altered genes identified in matched samples was 42.97% (0-100%) and 46.83% (0-100%), respectively (Table 2). Among the genomic alterations, 48 of them were in concordance between ctDNA and tumor tissue. Fifteen actionable alterations were identified in tissue defined according to the Oncobkb database, and 60% of them were shared in matched ctDNA (Fig. 5B). Notably, 41 of 91 (48.35%) alterations detected in ctDNA were not detected in the corresponding tissue sample. Specifically, 12 of them (27.27%) were oncogenic mutations and 3 of 44 (6.82%) could be identified as actionable, including a PIK3CA activated hot-spot, PTEN frameshift and KDM6A frameshift mutation.

Compared with UC patients in Western countries, more Chinese UC patients were diagnosed in the advanced stage for multiple reasons [9]. Meanwhile, fewer drugs were developed and approved in China for advanced UC which left no choice but only chemotherapy for most advanced Chinese UC patients. Meanwhile, because of the aristolochic acid exposure history, many Chinese UC patients, especially UTUC, tend to have chronic kidney disease, which made them unfit for platinum treatment [5]. Therefore, it’s of great importance to understand the genomic features of Chinese UC patients for further therapy development and clinical trials. Remarkably, over 60% of UC patients in this study were identified to have at least one potentially actionable somatic alteration, which would afford more choice for further treatment.

To date, FGFR2 and FGFR3 genes were the most actionable genes in UC, especially for UTUC, as erdafitinib (a FGFR inhibitor) was proved to have a 40% objective response rate in previously treated locally advanced and unresectable or metastatic UC with FGFR2/3 alterations [10]. We identified FGFRs gene alteration in 26.85% of UC patients, which was close to the corresponding ratio in the TCGA database [4]. Though may have an increased sensitivity to FGFR inhibitor, UC patients with FGFRs alterations may have a lower response rate to the ICIs therapy because of the suppressed infiltration of tumor immune cells in the tumor environment [11, 12]. Meanwhile, alterations in ERBB pathway, especially in ERBB2, raised increasing interest in UC recently, as 12.4% and 11% UCB patients had ERBB2 overexpressing (as tested by HER2 immunohistochemistry (IHC) staining) and mutations, respectively [13]. Similarly, ERBB2 alteration was observed in 10.71% of cases, which was equal to the data in Western UC patients[4]. An interesting correlation between ERBB2 gene mutations and a higher response possibility to platinum-based neoadjuvant chemotherapy was found in 61 muscle-invasive UCB [14]. Meanwhile, anti-Her2 therapy by Trastuzumab combined with chemotherapy has been proved to have an outstanding response rate and median overall survival of 70% and 14.1 months, respectively, in 44 advanced UC patients with HER2 overexpression in a single arm phase II trial [15]. Other anti-Her2 therapies, such as tyrosine kinase inhibitors, antibodies and antibody-drug conjugate, had been widely developed in UC with abnormal ERBB2 [16].

As previous work reported, DDR alterations were associated with a higher response rate and clinical benefit for both immune checkpoint inhibitors (ICIs), platinum-based neoadjuvant therapy and first-line chemotherapy in UC patients [17]. The previous study found 23.9% UCB patients had alterations in Homologous recombination repair gene pathway [18]. In our study, we found 47.32% and 14.29% UC patients had alterations and deleterious alterations in DDR pathway, respectively. The ratios were similar to the results analyzed by the panel involved the same genes [19]. Except for ICIs, tumors with deleterious DDR gene mutations, especially for BRCA1/2 gene, were also associated with better sensitivities with poly (ADP ribose) polymerase inhibitors (PARPi) [20]. Though it is still lack of evidence that proved the efficiency of PARPi in UC patients, PARPi combined with ICIs has been demonstrated to have cooperative effects in treating UC patients with HR mutations [21].

The prevalence of germline mutations of cancer susceptibility genes in patients with unselected UC was conflicting. Although previous studies established the point that UC was a carcinoma with rarely cancer susceptibility genes alterations, the latest research found that 14% of 586 unselected UC patients carried pathogenic or likely pathogenic germline variants, and 11.26% (66/586) of them had deleterious variants in DNA repair pathway [22]. Until now, the prevalence of germline mutations of cancer susceptibility genes in Chinese UC patients remains unclear. In our cohort, we only identified 1.79% of patients with pathogenic or likely pathogenic germline variants, which may represent a low prevalence of cancer susceptibility genes in Chinese UC patients compared to the corresponding Caucasian patients. In this study, we found a novel likely-pathogenic ERCC4 gene germline variants in a UTUC patient. Previously, ERCC4 gene mutations were identified in fanconi anemia, skin-photosensitive, nucleotide excision repair (NER)-deficient disorders xeroderma pigmentosum and XFE progeroid syndrome [23]. 2.03% of UC patients had alterations in ERCC4 gene, while no deleterious germline ERCC4 carrier of UC had been identified [24]. Meanwhile, Previous research found that 7%-8.3% unselected UTUC patients had lynch syndrome-related features, such as deficient mismatch repair (dMMR), microsatellite instability high (MSI-H) or deleterious alterations of MMR genes, while only 2.1% occurred in UC patients [22, 25]. In the present research, no germline variant in mismatch repair pathway was found, and the possible reasons may lie in the differences between Chinese and Western UC patients, limited UTUC patients enrolled and technology limitations (such as lack of detecting in MLH1 promoter hypermethylation and large rearrangements) [26].

Moreover, though previous studies suggested that ctDNA could serve as an effective biomarker in cancer diagnosis, risk stratification, therapy monitoring and early relapse in UC, the controversy about liquid biopsy remained [27]. Several prior studies published controversial results about the concordance levels between tissue and blood in other genitourinary carcinomas [28]. We found a concordance of 42.97% (0-100%) of the genetic alterations between 20 ctDNA and matched tissue samples, which was not reported before. Though factors, including tumor stage, metastasis status treatments, the interval time of sample collection and analyzed panel of genes would affect the concordance of genomic alterations between ctDNA and tissue, lipid biopsy is still an expanding way to overcome the intratumoral and intertumoral heterogeneity {Meeks, 2020 #632}. Our result support that genetic testing on tissue is still the gold standard for UC patients, meanwhile liquid biopsy would serve as a complementary source to provide additional and meaningful results to comprehend the genomic feature more precisely.

In this study, we identified a unique genomic feature of germline and somatic alterations in Chinese UC patients by next-generation sequencing. In total, 62.50% of 112 Chinese UC patients had at least one actionable genomic alteration, which would benefit from matched or related target therapies. Furthermore, our study found a good genomic concordance between ctDNA and matched tumor, suggesting the potential application of liquid biopsy in UC.

UC urothelial carcinoma

ICI immune checkpoint inhibitor

FGFR fibroblast growth factor receptor

FDA Food and Drug Administration

ctDNA cell-free tumor DNA

FFPE paraffin-embedded

EDTA ethylenediaminetetraacetic acid

cfDNA Cell-free DNA

GATK Genome Analysis Toolkit

SNV single nucleotide variation

inDel insertion and deletion

TCGA The Cancer Genome Atlas database

MSKCC Memorial-Sloan Kettering Cancer Center

SPSS Statistical Package for the Social Sciences

DDR DNA damage repair

ACMG American College of Medical Genetics and Genomics

UTUC upper tract urothelial carcinoma

UCB urothelial carcinoma of bladder

MMR mismatch repair

dMMR deficient mismatch repair

NER nucleotide excision repair

MSI-H microsatellite instability high

Ethics approval and consent to participate

Allthe subjects have signed informed consent for inclusion before participating in the study. The study was performed in accordance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of PLA General Hospital for Clinical Investigation.

Consent for publication

Not applicable.

Availability of data and material

All data generated or analysed during this study are included in this published article and its supplementary information files.

Competing Interest

The authors indicated no financial relationship.

Funding

This work was supported by the Chinese People's Liberation Army General Hospital Medical Big Data R&D Project (No: 2017MBD-012).

Author Contributions

BY, XZ and CW contributed equally to this work.

Acknowledgements

Not applicable

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Table 1 Demographic and clinical data of patients
Characteristics		n=112
Median age (range)		67 (25-86)
Sex
	Male	81
	Female	31
Smoking
	Current	19
	Former	37
	None	56
Tumor Stage
	T1	17
	T2	43
	T3	27
	T4	19
	Ta	6
Classification
	Upper tract	31
	Bladder	81
Sample Type	Blood	34
	Tumor	78

Table 2. Genomic alterations identified in matched tissue and blood
Patient number	Genomic alterations in tissue number	Genomic alterations in blood number	Genes altered in both samples, number (%)	Genomic alterations in both samples, number (%)
P003	6	5	5 (83.3%)	5 (83.3%)
P009	2	7	2 (28.57%)	2 (28.57%)
P020	0	10	0	0
P024	2	2	0	0
P035	1	1	1 (100%)	1 (100%)
P043	4	3	0	0
P053	5	9	5 (62.5%)	3 (27.27%)
P054	4	4	4 (100%)	4 (100%)
P071	3	4	2 (50%)	2 (40%)
P072	3	3	3 (100%)	3 (100%)
P073	3	3	3 (100%)	3 (100%)
P074	15	10	4 (36.36%)	6 (30%)
P077	5	5	4 (66.67%)	4 (66.67%)
P084	17	4	2 (13.33%)	2 (9.52%)
P095	4	7	4 (57.14%)	4 (57.14%)
P096	4	1	0	0
P109	9	11	7 (63.64%)	7 (63.64%)
P110	3	1	1 (50%)	1 (33.33%)
P111	4	0	0	0
P112	5	1	1 (25%)	1 (20%)

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Journal Publication

published 15 Feb, 2021

Read the published version in BMC Cancer →

Review #2 received at journal
20 Nov, 2020
Editorial decision: Major revision
20 Nov, 2020
Reviewer #2 agreed at journal
09 Nov, 2020
Review #1 received at journal
28 Sep, 2020
Reviewer #1 agreed at journal
03 Sep, 2020
Reviewers invited by journal
10 Aug, 2020
Editor assigned by journal
07 Aug, 2020
Submission checks completed at journal
30 Jul, 2020
Editor invited by journal
29 Jul, 2020
First submitted to journal
24 Jul, 2020

You are reading this latest preprint version

Genomic Profiling of Chinese Urothelial Carcinoma Patients

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Background

Methods

Samples source and ethic data

Dna Isolation

Target Next-generation Sequencing

Data Processing

Statistical analysis

Results

Demographic and clinical data

Somatic Alterations In Chinese Uc Patients

Germline Alteration

Differences Of Somatic Gene Alterations Between Utuc And Ucb

Genomic Alterations In Fgfr Genes

Genomic Alterations In Erbb Family

Somatic Alterations In Dna Repair Pathway

Discussion

Conclusion

Abbreviations

Declarations

References

Tables

Supplementary Files

Status:

Journal Publication

Version 1