Cancer Research and Treatment

Original Article

Genitourinary cancer

Clear Cell Adenocarcinoma of Urethra: Clinical and Pathologic Implications and Characterization of Molecular Aberrations: Boram Song, Seok Hyun Lee, Jeong Hwan Park, Kyung Chul Moon; Cancer Res Treat. 2024;56(1):280-293. Published online September 11, 2023; DOI: https://doi.org/10.4143/crt.2023.577

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Purpose
This study aimed to evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets.
Materials and Methods
We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways.
Results
All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, and PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, and CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, mitogen-activated protein kinase signaling pathway, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Wnt/β-catenin pathway) as candidates for targeted therapies.
Conclusion
Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.

Citations

Citations to this article as recorded by

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