Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder

Isharwal, Sumit; Hu, Wenhuo; Sarungbam, Judy; Chen, Ying-Bei; Gopalan, Anuradha; Fine, Samson W.; Tickoo, Satish K.; Sirintrapun, S. Joseph; Jadallah, Sana; Loo, Florence L.; Pietzak, Eugene J.; Eugene, K.; Bochner, Bernard H.; Berger, Michael F.; Iyer, Gopa; Solit, David B.; Reuter, Victor E.; Al‐Ahmadie, Hikmat

doi:10.1002/path.5261

Cited by 42 publications

(43 citation statements)

References 25 publications

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“…Urothelial carcinomas with HRAS / KRAS mutations also seem to have enriched mutations at the TERT promoter region as well as mutations at various TP53 /cell cycle genes . It has been observed repeatedly that mutations at the FGFR3 , PI3KCA , and TERT genes are present in the majority of the low‐grade urothelial carcinomas, whereas mutations involving the MAPK/ERK pathway, mainly HRAS , KRAS and occasionally BRAF , have been identified in UPs and IUPs .…”

Section: Molecular Studies Investigating Iupmentioning

confidence: 99%

“…Several groups of investigators, using cohorts of various sizes and a variety of methodologies, have studied the genomic landscape of IUP (Table 1) [5][6][7][8][9][10]. In a recent issue of The Journal of Pathology, Isharwal and colleagues reported the findings from the most recent of such efforts.…”

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confidence: 99%

“…The vast majority of IUPs and UPs did not show mutations in FGFR3, TERT, TP53, RB1, or chromatin remodeling genes, which are known to be common mutations in urothelial carcinoma. Urothelial carcinomas with HRAS/KRAS mutations also seem to have enriched mutations at the TERT promoter region as well as mutations at various TP53/cell cycle genes [9][10][11][12]. It has been observed repeatedly that mutations at the FGFR3, PI3KCA, and TERT Genomic landscape of benign papillary lesions 5 genes are present in the majority of the low-grade urothelial carcinomas, whereas mutations involving the MAPK/ERK pathway, mainly HRAS, KRAS and occasionally BRAF, have been identified in UPs and IUPs [8,10].…”

mentioning

confidence: 99%

“…Urothelial carcinomas with HRAS/KRAS mutations also seem to have enriched mutations at the TERT promoter region as well as mutations at various TP53/cell cycle genes [9][10][11][12]. It has been observed repeatedly that mutations at the FGFR3, PI3KCA, and TERT Genomic landscape of benign papillary lesions 5 genes are present in the majority of the low-grade urothelial carcinomas, whereas mutations involving the MAPK/ERK pathway, mainly HRAS, KRAS and occasionally BRAF, have been identified in UPs and IUPs [8,10]. In the current study, all IUPs (10 HRAS and 1 KRAS mutations) and 91% of UPs (8 KRAS and 2 HRAS) had MAPK/ERK pathway mutations and no papilloma harbored TP53 mutations [10].…”

mentioning

confidence: 99%

“…It has been observed repeatedly that mutations at the FGFR3, PI3KCA, and TERT Genomic landscape of benign papillary lesions 5 genes are present in the majority of the low-grade urothelial carcinomas, whereas mutations involving the MAPK/ERK pathway, mainly HRAS, KRAS and occasionally BRAF, have been identified in UPs and IUPs [8,10]. In the current study, all IUPs (10 HRAS and 1 KRAS mutations) and 91% of UPs (8 KRAS and 2 HRAS) had MAPK/ERK pathway mutations and no papilloma harbored TP53 mutations [10]. The findings in the current study are comparable to those of a previous study [8].…”

mentioning

confidence: 99%

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Distinct mutational landscape of inverted urothelial papilloma

Akgul

MacLennan

Cheng

2019

The Journal of Pathology

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A recent study has identified gene mutations involving the MAPK/ERK pathway, particularly the HRAS gene, in all inverted urothelial papillomas (IUPs), in the absence of pathway mutations in TERT promoter, FGFR3, and TP53/RB1genes. Neither recurrence nor progression was observed in IUPs. These data support several longstanding hypotheses: (1) IUPs are benign and do not recur or progress; (2) they harbor mutations that are different from those of urothelial carcinoma; and (3) they arise through different molecular mechanisms than low‐ or high‐grade urothelial carcinoma. As the most critical differential diagnosis in this context is inverted‐type urothelial carcinoma, more comprehensive studies are needed to compare and contrast these entities. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Molecular Studies Investigating Iupmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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Distinct mutational landscape of inverted urothelial papilloma

Akgul

MacLennan

Cheng

2019

The Journal of Pathology

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Frequent KRAS and HRAS mutations in squamous cell papillomas of the head and neck

Sasaki

Masago

Hanai

et al. 2020

The Journal of Pathology CR

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Squamous cell papilloma (SCP) is a benign neoplasm of the head and neck. Human papillomavirus (HPV) has been reported to be a tumourigenic factor for SCP. However, not all SCPs are positive for HPV, suggesting that other possible mechanisms are involved in their development. In this study, we examined the mutational status of 51 SCPs using targeted panel sequencing in addition to HPV status using GP5+/GP6+ PCR. HPV DNA was detected in 6 (12%) SCPs, while KRAS and HRAS mutations were detected in 18 (35%) and 17 (33%) SCPs, respectively. Notably, KRAS mutations, HRAS mutations and HPV infection were mutually exclusive. The larynx and trachea (4/7, 57%) were more preferentially infected by HPV than the other sites (2/44, 5%, p = 0.0019) and HPV was associated with multifocal development (4/5, 80%). In contrast, KRAS and HRAS mutations in SCPs were evenly distributed across the anatomical sites and found only in single SCPs. In conclusion, this study demonstrated that HPV was not frequently involved in SCPs and that RAS mutations were more common alterations. In contrast to inverted sinonasal papillomas and oncocytic sinonasal papillomas, SCP may not be a precursor lesion of carcinoma, because these aetiological events in SCP are distinct from squamous cell carcinoma in the same sites.

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Inverted urothelial papilloma and urothelial carcinoma with inverted growth are histologically and molecularly distinct entities

Almassi

Pietzak

Sarungbam

et al. 2020

The Journal of Pathology

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Inverted urothelial papilloma and urothelial carcinoma with inverted growth are histologically and molecularly distinct entities We read with great interest the invited commentary by Akgul et al [1] on our report on the genomic landscape of urothelial papilloma (UP) and inverted urothelial papilloma (IUP) published in a recent issue of The Journal of Pathology [2]. The authors highlighted the salient findings of our study, namely that IUP and UP have genomic profiles that are distinct from urothelial carcinomas (UC). Unlike UC, IUP and UP have low tumor mutational burden and do not exhibit a predominant APOBEC mutation signature. Furthermore, oncogenic alterations in HRAS and KRAS were present in nearly all cases of IUP and UP, whereas alterations common to UC, including mutations in FGFR3, TP53, chromatin-modifying genes and the TERT promoter, were rarely observed. An important point raised by the authors was the lack of comparison between the molecular profiles of IUP and non-invasive UC with inverted growth pattern (IUC), as these entities have overlapping histologic features and may be difficult to distinguish based on histologic review alone. To address this insightful question raised by Akgul

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Genomic landscape of inverted urothelial papilloma and urothelial papilloma of the bladder

Cited by 42 publications

References 25 publications

Distinct mutational landscape of inverted urothelial papilloma

Distinct mutational landscape of inverted urothelial papilloma

Frequent KRAS and HRAS mutations in squamous cell papillomas of the head and neck

Inverted urothelial papilloma and urothelial carcinoma with inverted growth are histologically and molecularly distinct entities

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