Genomic Characterization of Prostatic Basal Cell Carcinoma

Jin Yih Low; Minjeong Ko; Brian Hanratty; Radhika A. Patel; Akshay Bhamidipati; Christopher M. Heaphy; Erolcan Sayar; John K. Lee; Shan Li; Angelo M. De Marzo; William G. Nelson; Anuj Gupta; Srinivasan Yegnasubramanian; Gavin Ha; Jonathan I. Epstein; Michael C. Haffner

doi:10.1016/j.ajpath.2022.09.010

Genomic Characterization of Prostatic Basal Cell Carcinoma

Jin Yih Low, Minjeong Ko, Brian Hanratty, Radhika A. Patel, Akshay Bhamidipati, Christopher M. Heaphy, Erolcan Sayar, John K. Lee, Shan Li, Angelo M. De Marzo, William G. Nelson, Anuj Gupta, Srinivasan Yegnasubramanian, Gavin Ha, Jonathan I. Epstein, Michael C. Haffner

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Basal cell carcinoma (BCC) of the prostate is a rare tumor. Compared with the more common acinar adenocarcinoma (AAC) of the prostate, BCCs show features of basal cell differentiation and are thought to be biologically distinct from AAC. The spectrum of molecular alterations of BCC has not been comprehensively described, and genomic studies are lacking. Herein, whole genome sequencing was performed on archival formalin-fixed, paraffin-embedded specimens of two cases with BCC. Prostatic BCCs were characterized by an overall low copy number and mutational burden. Recurrent copy number loss of chromosome 16 was observed. In addition, putative driver gene alterations in KIT, DENND3, PTPRU, MGA, and CYLD were identified. Mechanistically, depletion of the CYLD protein resulted in increased proliferation of prostatic basal cells in vitro. Collectively, these studies show that prostatic BCC displays distinct genomic alterations from AAC and highlight a potential role for loss of chromosome 16 in the pathogenesis of this rare tumor type.

Original language	English (US)
Pages (from-to)	4-10
Number of pages	7
Journal	American Journal of Pathology
Volume	193
Issue number	1
DOIs	https://doi.org/10.1016/j.ajpath.2022.09.010
State	Published - Jan 2023

ASJC Scopus subject areas

Pathology and Forensic Medicine

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Low, J. Y., Ko, M., Hanratty, B., Patel, R. A., Bhamidipati, A., Heaphy, C. M., Sayar, E., Lee, J. K., Li, S., De Marzo, A. M., Nelson, W. G., Gupta, A., Yegnasubramanian, S., Ha, G., Epstein, J. I., & Haffner, M. C. (2023). Genomic Characterization of Prostatic Basal Cell Carcinoma. American Journal of Pathology, 193(1), 4-10. https://doi.org/10.1016/j.ajpath.2022.09.010

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title = "Genomic Characterization of Prostatic Basal Cell Carcinoma",

abstract = "Basal cell carcinoma (BCC) of the prostate is a rare tumor. Compared with the more common acinar adenocarcinoma (AAC) of the prostate, BCCs show features of basal cell differentiation and are thought to be biologically distinct from AAC. The spectrum of molecular alterations of BCC has not been comprehensively described, and genomic studies are lacking. Herein, whole genome sequencing was performed on archival formalin-fixed, paraffin-embedded specimens of two cases with BCC. Prostatic BCCs were characterized by an overall low copy number and mutational burden. Recurrent copy number loss of chromosome 16 was observed. In addition, putative driver gene alterations in KIT, DENND3, PTPRU, MGA, and CYLD were identified. Mechanistically, depletion of the CYLD protein resulted in increased proliferation of prostatic basal cells in vitro. Collectively, these studies show that prostatic BCC displays distinct genomic alterations from AAC and highlight a potential role for loss of chromosome 16 in the pathogenesis of this rare tumor type.",

author = "Low, {Jin Yih} and Minjeong Ko and Brian Hanratty and Patel, {Radhika A.} and Akshay Bhamidipati and Heaphy, {Christopher M.} and Erolcan Sayar and Lee, {John K.} and Shan Li and {De Marzo}, {Angelo M.} and Nelson, {William G.} and Anuj Gupta and Srinivasan Yegnasubramanian and Gavin Ha and Epstein, {Jonathan I.} and Haffner, {Michael C.}",

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year = "2023",

month = jan,

doi = "10.1016/j.ajpath.2022.09.010",

language = "English (US)",

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T1 - Genomic Characterization of Prostatic Basal Cell Carcinoma

AU - Low, Jin Yih

AU - Ko, Minjeong

AU - Hanratty, Brian

AU - Patel, Radhika A.

AU - Bhamidipati, Akshay

AU - Heaphy, Christopher M.

AU - Sayar, Erolcan

AU - Lee, John K.

AU - Li, Shan

AU - De Marzo, Angelo M.

AU - Nelson, William G.

AU - Gupta, Anuj

AU - Yegnasubramanian, Srinivasan

AU - Ha, Gavin

AU - Epstein, Jonathan I.

AU - Haffner, Michael C.

PY - 2023/1

Y1 - 2023/1

N2 - Basal cell carcinoma (BCC) of the prostate is a rare tumor. Compared with the more common acinar adenocarcinoma (AAC) of the prostate, BCCs show features of basal cell differentiation and are thought to be biologically distinct from AAC. The spectrum of molecular alterations of BCC has not been comprehensively described, and genomic studies are lacking. Herein, whole genome sequencing was performed on archival formalin-fixed, paraffin-embedded specimens of two cases with BCC. Prostatic BCCs were characterized by an overall low copy number and mutational burden. Recurrent copy number loss of chromosome 16 was observed. In addition, putative driver gene alterations in KIT, DENND3, PTPRU, MGA, and CYLD were identified. Mechanistically, depletion of the CYLD protein resulted in increased proliferation of prostatic basal cells in vitro. Collectively, these studies show that prostatic BCC displays distinct genomic alterations from AAC and highlight a potential role for loss of chromosome 16 in the pathogenesis of this rare tumor type.

AB - Basal cell carcinoma (BCC) of the prostate is a rare tumor. Compared with the more common acinar adenocarcinoma (AAC) of the prostate, BCCs show features of basal cell differentiation and are thought to be biologically distinct from AAC. The spectrum of molecular alterations of BCC has not been comprehensively described, and genomic studies are lacking. Herein, whole genome sequencing was performed on archival formalin-fixed, paraffin-embedded specimens of two cases with BCC. Prostatic BCCs were characterized by an overall low copy number and mutational burden. Recurrent copy number loss of chromosome 16 was observed. In addition, putative driver gene alterations in KIT, DENND3, PTPRU, MGA, and CYLD were identified. Mechanistically, depletion of the CYLD protein resulted in increased proliferation of prostatic basal cells in vitro. Collectively, these studies show that prostatic BCC displays distinct genomic alterations from AAC and highlight a potential role for loss of chromosome 16 in the pathogenesis of this rare tumor type.

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Genomic Characterization of Prostatic Basal Cell Carcinoma

Abstract

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