title: Genetic mutations associated with metastatic clear cell renal cell carcinoma.
abstract: Metastasis is the major cause of death among cancer patients, yet early detection and intervention of metastasis could significantly improve their clinical outcomes. We have sequenced and analyzed RNA (Expression) and DNA (Mutations) from the primary tumor (PT), tumor extension (TE) and lymphatic metastatic (LM) sites of patients with clear cell renal cell carcinoma (CCRCC) before treatment. Here, we report a three-nucleotide deletion near the C-region of Plk5 that is specifically associated with the lymphatic metastasis. This mutation is un-detectable in the PT, becomes detectable in the TE and dominates the LM tissue. So while only a few primary cancer cells carry this mutation, the majority of metastatic cells have this mutation. The increasing frequency of this mutation in metastatic tissue suggests that this Plk5 deletion could be used as an early indicator of CCRCC metastasis, and be identified by low cost PCR assay. A large scale clinical trial could reveal whether a simple PCR assay for this mutation at the time of nephrectomy could identify and stratify high-risk CCRCC patients for treatments.
authors.affiliation: Department of Blood Transfusion, Second Affiliated Hospital, Third Military Medical University, Chongqing, P. R. China.|Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hao
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Qingjian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Blood Transfusion, Second Affiliated Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Fengjie
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Kaijin
authors.initials: K
authors.lastname: Wu
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Cunye
authors.initials: C
authors.lastname: Qu
authors.affiliation: Bioinformatics Service, Norris Medical Library, University of Southern California, Los Angeles, CA, USA.
authors.forename: Yibu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Bioinformatics Service, Norris Medical Library, University of Southern California, Los Angeles, CA, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Chen
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Andres
authors.initials: A
authors.lastname: Stucky
authors.affiliation: Z-Genetic Medicine LLC, Temple City, CA, USA.
authors.forename: Jiangjian
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Urology, Second Affiliated Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Longkun
authors.initials: L
authors.lastname: Li
authors.affiliation: Ostrow School of Dentistry and Department of Pediatrics, School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Jiang F
authors.initials: JF
authors.lastname: Zhong
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C549900:polo-like kinase 5, human
keywords: Plk5; metastasis-specific mutation; renal cell carcinoma