Mutational Context and Diverse Clonal Development in Early and Late Bladder Cancer

Nordentoft, Iver; Lamy, Philippe; Birkenkamp‐Demtröder, Karin; Shumansky, Karey; Vang, Søren; Hornshøj, Henrik; Juul, Malene; Villesen, Palle; Hedegaard, Jakob; Roth, Andrew; Thorsen, Kasper; Høyer, Søren; Borre, Michael; Reinert, Thomas; Fristrup, Niels; Dyrskjøt, Lars; Shah, Sohrab P.; Pedersen, Jakob Skou; Ørntoft, Torben F.

doi:10.1016/j.celrep.2014.04.038

Cited by 131 publications

(127 citation statements)

References 37 publications

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“…Because it is likely that tumours develop from areas of premalignant urothelial cells, it is not surprising that multifocal and metachronous tumours show common as well as novel uniquely acquired mutations [107][108][109]. Copy number abnormalities, loss of heterozygosity, and increased genomic instability have been associated with increasing tumour grade and stage.…”

Section: Genomics Of Urothelial Carcinomamentioning

confidence: 99%

“…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%

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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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Section: Genomics Of Urothelial Carcinomamentioning

confidence: 99%

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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“…In bladder cancer, A3 mutations are enriched in highly transcribed genes, particularly on the sense strand [69], suggesting that A3s also act on ssDNA during transcription.…”

Section: Availability Of Ssdna Substratementioning

confidence: 99%

“…Analysis of metachronous paired samples representing early superficial noninvasive (Ta) and subsequent invasive (T1/T2) bladder tumors both displayed the A3 signature equally [69]. In breast cancers, A3 mutations begin to accumulate early but make a greater contribution to the mutational load (particularly C>G transversions) of later subclones, suggesting an increasing fraction of A3 mutagenesis as the tumors evolve [60].…”

Section: A3 Mutations: Passengers or Drivers?mentioning

confidence: 99%

APOBEC3 genes: retroviral restriction factors to cancer drivers

Henderson

Fenton

2015

Trends in Molecular Medicine

102

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Abstract:The APOBEC3 cytosine deaminases play key roles in innate immunity through their ability to mutagenize viral DNA and restrict viral replication. Now recent advances in cancer genomics together with biochemical characterization of the APOBEC3 enzymes have implicated at least two family members in somatic mutagenesis during tumor development. Here we review the evidence linking these enzymes to carcinogenesis and highlight key questions, including the potential mechanisms that misdirect APOBEC3 activity to the host genome, the links to viral infection, and the association between a common APOBEC3 polymorphism and cancer risk. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationHenderson and Fenton: highlights AbstractThe APOBEC3 cytosine deaminases play key roles in innate immunity through their

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“…Mutations produced by APOBEC3A/B have known properties confirmed both in yeast and in human cancers: (1) They are C→D mutations in the TpCpN context (the more specific APOBEC3A/B signature is TpCpW→K, where D denotes A, T, or G; W denotes A or T; and K denotes G or T) (Burns et al 2013a;Taylor et al 2013;Chan et al 2015;Seplyarskiy et al 2016); (2) they often form strand-coordinated clusters (Nik-Zainal et al 2012;Roberts et al 2013;Taylor et al 2013); (3) they are strongly biased toward the lagging strand during replication (Haradhvala et al 2016;Hoopes et al 2016;Morganella et al 2016;Nik-Zainal et al 2016;Seplyarskiy et al 2016); (4) they are biased toward the nontranscribed strand, at least in breast and bladder cancer (Nordentoft et al 2014;Morganella et al 2016); and (5) cytosines deaminated to uracils by APOBEC frequently result in C→G substitutions. According to the current models, these mutations arise due to incomplete repair of U-G mismatches resulting in abasic sites.…”

mentioning

confidence: 99%

APOBEC3A/B-induced mutagenesis is responsible for 20% of heritable mutations in the TpCpW context

2016

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APOBEC3A/B cytidine deaminase is responsible for the majority of cancerous mutations in a large fraction of cancer samples. However, its role in heritable mutagenesis remains very poorly understood. Recent studies have demonstrated that both in yeast and in human cancerous cells, most APOBEC3A/B-induced mutations occur on the lagging strand during replication and on the nontemplate strand of transcribed regions. Here, we use data on rare human polymorphisms, interspecies divergence, and de novo mutations to study germline mutagenesis and to analyze mutations at nucleotide contexts prone to attack by APOBEC3A/B. We show that such mutations occur preferentially on the lagging strand and on nontemplate strands of transcribed regions. Moreover, we demonstrate that APOBEC3A/B-like mutations tend to produce strandcoordinated clusters, which are also biased toward the lagging strand. Finally, we show that the mutation rate is increased 3 ′ of C→G mutations to a greater extent than 3 ′ of C→T mutations, suggesting pervasive trans-lesion bypass of the APOBEC3A/B-induced damage. Our study demonstrates that 20% of C→T and C→G mutations in the TpCpW context-where W denotes A or T, segregating as polymorphisms in human population-or 1.4% of all heritable mutations are attributable to APOBEC3A/B activity.

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Mutational Context and Diverse Clonal Development in Early and Late Bladder Cancer

Cited by 131 publications

References 37 publications

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

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

APOBEC3 genes: retroviral restriction factors to cancer drivers

APOBEC3A/B-induced mutagenesis is responsible for 20% of heritable mutations in the TpCpW context

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