Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation

Guo, Guangwu; Sun, Xiaojuan; Chen, Chao; Wu, Song; Huang, Peide; Li, Zesong; Dean, Michael; Huang, Yi; Jia, Wenlong; Zhou, Quan; Tang, Aifa; Yang, Zuoquan; Li, Xianxin; Song, Pengfei; Zhao, Xiaokun; Ye, Rui; Zhang, Shiqiang; Zhao, Lin; Qi, Mingfu; Wan, Shengqing; Xie, Liangfu; Fan, Fan; Nickerson, Michael L.; Zou, Xiangjun; Hu, Xueda; Li, Xing; Lv, Zhaojie; Mei, Hongbin; Gao, Shengjie; Liang, Chaozhao; Gao, Zhibo; Lu, Jingxiao; Yu, Yuan; Liu, Chunxiao; Lin, Liang-In; Fang, Xiaodong; Jiang, Ziyu; Yang, Jie; Li, Cailing; Zhao, Xin; Chen, Jing; Zhang, Fang; Lai, Y Y; Lin, Zheguang; Zhou, Fangjian; Chen, Hao; Chan, Hsiao Chang; Tsang, Shirley; Theodorescu, Dan; Li, Yingrui; Zhang, Xiuqing; Wang, Jian; Yang, Huanming; Gui, Yaoting; Wang, Jun; Cai, Zhiming

doi:10.1038/ng.2798

Cited by 411 publications

(410 citation statements)

References 38 publications

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“…Finally, the ERBB2 mutation in case 14 is a previously confirmed somatic oncogenic mutation (SIFT score of 0) in breast, ovarian, and bladder carcinoma. [35][36][37] The observed BRAF mutation frequency in mixed desmoplastic malignant 23 reporting a 6% BRAF mutation rate in mixed desmoplastic malignant melanoma (but an absence of BRAF mutations in pure desmoplastic malignant melanoma in accordance with our data). The higher percentage of BRAF mutations in the present study in mixed desmoplastic malignant melanoma might be explained by an increased sensitivity due to manual microdissection of tumors.…”

Section: Mutations In Desmoplastic Melanomasupporting

confidence: 91%

Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis

et al. 2015

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Desmoplastic malignant melanoma is a distinct melanoma entity histologically subtyped into mixed and pure forms due to significantly reduced lymph node metastases in the pure form. Recent reports investigating common actionable driver mutations have demonstrated a lack of BRAF, NRAS, and KIT mutation in pure desmoplastic melanoma. In search for alternative driver mutations next generation amplicon sequencing for hotspot mutations in 50 genes cardinal to tumorigenesis was performed and in addition the RET G691S polymorphism was investigated. Data from 21 desmoplastic melanomas (12 pure and 9 mixed) were retrieved. Pure desmoplastic melanomas were either devoid of mutations (50%) or displayed mutations in tumor suppressor genes (TP53, CDKN2A, and SMAD4) singularly or in combination with the exception of a PIK3CA double-mutation lacking established biological relevance. Mixed desmoplastic melanomas on the contrary were frequently mutated (89%), and 67% exhibited activating mutations similar to common-type cutaneous malignant melanomas (BRAF, NRAS, FGFR2, and ERBB2). Separate analysis of morphologically heterogeneous tumor areas in four mixed desmoplastic malignant melanomas displayed no difference in mutation status and RET G691 status. GNAQ and GNA11, two oncogenes in BRAF and NRAS wild-type uveal melanomas, were not mutated in our cohort. The RET G691S polymorphism was found in 25% of pure and 38% of mixed desmoplastic melanomas. Apart from RET G691S our findings demonstrate absence of activating driver mutations in pure desmoplastic melanoma beyond previously investigated oncogenes (BRAF, NRAS, and KIT). The findings underline the therapeutic dichotomy of mixed versus pure desmoplastic melanoma with regard to activating mutations primarily of the mitogen-activated protein kinase pathway.

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Section: Mutations In Desmoplastic Melanomasupporting

confidence: 91%

Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis

et al. 2015

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“…Such trends will undoubtedly continue in the years to come. It will also be important to determine to what extent mutations or misregulation of cohesin and condensin subunits might contribute to human cancers (Ham et al 2007;Balbás-Martínez et al 2013;Guo et al 2013;Kon et al 2013;Solomon et al 2013). Third, and, finally, all issues described above need to be addressed, also, from an evolutionary point of view.…”

Section: Discussionmentioning

confidence: 99%

Chromosome Dynamics during Mitosis

Hirano

2015

Cold Spring Harb Perspect Biol

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The primary goal of mitosis is to partition duplicated chromosomes into daughter cells. Eukaryotic chromosomes are equipped with two distinct classes of intrinsic machineries, cohesin and condensins, that ensure their faithful segregation during mitosis. Cohesin holds sister chromatids together immediately after their synthesis during S phase until the establishment of bipolar attachments to the mitotic spindle in metaphase. Condensins, on the other hand, attempt to "resolve" sister chromatids by counteracting cohesin. The products of the balancing acts of cohesin and condensins are metaphase chromosomes, in which two rod-shaped chromatids are connected primarily at the centromere. In anaphase, this connection is released by the action of separase that proteolytically cleaves the remaining population of cohesin. Recent studies uncover how this series of events might be mechanistically coupled with each other and intricately regulated by a number of regulatory factors.

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“…Although TERT mutations are present in up to 79% of bladder neoplasms, they have no association with clinical outcome; however, its presence can be of great diagnostic utility, given the relative rarity of this mutation in other tumours that may have overlapping histology. Next-generation sequencing efforts have demonstrated that the mutational landscape of urothelial tumours are quite complex, with >300 mutations, >200 copy number alterations, and >20 rearrangements per tumour [108,[115][116][117]. Only lung cancer has been shown to harbour a higher rate of mutations, although most are certainly passenger mutations with no functional consequence [118].…”

Section: Genomics Of Urothelial Carcinomamentioning

confidence: 99%

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

et al. 2016

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It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of "usual type" urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report. PATIENT SUMMARY Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 World Health Organization classification. Better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential. v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j AbstractIt has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours.

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Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation

Cited by 411 publications

References 38 publications

Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis

Mutational dichotomy in desmoplastic malignant melanoma corroborated by multigene panel analysis

Chromosome Dynamics during Mitosis

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

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