By Ian Demsky | 14 April | labblog.uofmhealth.org/lab-report
Renal cell carcinoma is the most common type of kidney cancer, accounting for about 90% of cases in adults. But there are more than 10 different subtypes, each with important differences at a molecular level that can shape their aggressiveness or their response to treatment.
Using next-generation RNA sequencing techniques, a team of scientists from the University of Michigan Rogel Cancer Center has uncovered the gene signature of chromophobe renal cell carcinoma (ChRCC) and have extensively tested the expression of three new biomarkers. The subtype is the third most common type of renal cell carcinoma, comprising about 5% of cases.
The U-M analysis, which appears in European Urology, examined RNA sequencing data from more than 1,000 kidney cancer samples combining profiles from Michigan Medicine patients with others in The Cancer Genome Atlas.
“Our approach identified two genes — Forkhead Box I1 (FOXI1) and Rh family C glycoprotein (RHCG) — and one long non-coding RNA (LINC01187) that are overexpressed in chromophobe renal cell carcinoma and positive in related oncocytic tumors,” says senior study author Rohit Mehra, MD, an associate professor of pathology at Michigan Medicine and member of the Michigan Center for Translational Pathology.
“We investigated both cancers primary to the kidney as well as those which had spread out, and found strong expression of these three biomarkers,” he adds. “Importantly, we did not find them to be associated with other subtypes of kidney cancer, especially in metastatic state.”
Follow-up work is being conducted to validate the new biomarkers for use in the clinic at U-M and beyond, Mehra notes, where they may be particularly useful in diagnosis of metastatic tumors or a subset of primary tumors that can’t be readily identified under the microscope.
The success of the group’s integrative sequencing analysis approach is helping them develop a more specific kidney cancer diagnostic panel to complement existing tools, Mehra says. He notes the approach allowed the group previously to identify a specific biomarker for another rare kidney cancer called mucinous tubular and spindle cell carcinoma, helping to aid the diagnosis of challenging samples from U-M and other institutions.
"Our approach identified two genes — Forkhead Box I1 (FOXI1) and Rh family C glycoprotein (RHCG) — and one long non-coding RNA (LINC01187) that are overexpressed in chromophobe renal cell carcinoma."Rohit Mehra, MD
The current analysis also points toward the type of cell within a normal kidney from where chromophobe renal cell carcinoma and related cancers originate — a specialized cell in the lining of the small tubules in the kidneys called an intercalated cell. This information could be helpful in future efforts to treat or better classify these tumors.
Importantly, the study also throws light on possible mechanisms that may underlie a variant of the disease called sarcomatoid ChRCC, where the scientists observed a complete lack of FOXI1 and long non-coding RNA. Loss of FOXI1, a key transcription factor, may contribute to de-differentiation in these tumors which tend to be more aggressive and may require additional therapeutic strategies.
The research was led by co-first authors Stephanie Skala, MD, Xiaoming Wang, PhD, Yuping Zhang, PhD, and Rahul Mannan, MBBS. The other senior authors include Arul Chinnaiyan, MD, PhD, and Saravana Dhanasekaran, PhD.
The study was supported by the Michigan Prostate SPORE (2P50CA186786-06), National Cancer Institute (1U01CA214170-01, 1R35CA231996-01) and Michigan Medicine Department of Pathology.
Paper cited: “Next-Generation RNA Sequencing-Based Biomarker Characterization of Chromophobe Renal Cell Carcinoma and Related Oncoyctic Neoplasms,” European Urology. DOI: 10.1016/j.eururo.2020.03.003
—
This story was written by Ian Demsky and originally appeared in the Michigan Medicine Health Lab Blog on 04.14.2020.
ON THE COVER
Breast team reviewing a patient's slide. (From left to right) Ghassan Allo, Fellow; Laura Walters, Clinical Lecturer; Celina Kleer, Professor. See Article 2014Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Autopsy Technician draws blood while working in the Wayne County morgue. See Article 2016Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Dr. Sriram Venneti, MD, PhD and Postdoctoral Fellow, Chan Chung, PhD investigate pediatric brain cancer. See Article 2017Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Director of the Neuropathology Fellowship, Dr. Sandra Camelo-Piragua serves on the Patient and Family Advisory Council. 2018Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Residents Ashley Bradt (left) and William Perry work at a multi-headed scope in our new facility. 2019Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Dr. Kristine Konopka (right) instructing residents while using a multi-headed microscope. 2020Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Patient specimens poised for COVID-19 PCR testing. 2021Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Dr. Pantanowitz demonstrates using machine learning in analyzing slides. 2022Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
(Left to Right) Drs. Angela Wu, Laura Lamps, and Maria Westerhoff. 2023Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
ON THE COVER
Illustration representing the various machines and processing used within our labs. 2024Department Chair |
newsletter
INSIDE PATHOLOGYAbout Our NewsletterInside Pathology is an newsletter published by the Chairman's Office to bring news and updates from inside the department's research and to become familiar with those leading it. It is our hope that those who read it will enjoy hearing about those new and familiar, and perhaps help in furthering our research. CONTENTS
|
MLabs, established in 1985, functions as a portal to provide pathologists, hospitals. and other reference laboratories access to the faculty, staff and laboratories of the University of Michigan Health System’s Department of Pathology. MLabs is a recognized leader for advanced molecular diagnostic testing, helpful consultants and exceptional customer service.