Genomic profiles of renal cell carcinoma in a small Chinese cohort

Sheng Tai; Dan-Dan Xu; Zhixian Yu; Yu Guan; Shuiping Yin; Jun Xiao; Song Xue; Chaozhao Liang

doi:10.3389/fonc.2023.1095775

Genomic profiles of renal cell carcinoma in a small Chinese cohort

Front Oncol. 2023 Jun 22:13:1095775. doi: 10.3389/fonc.2023.1095775. eCollection 2023.

Authors

Sheng Tai^{1

2

3}, Dan-Dan Xu^{4

5}, Zhixian Yu⁶, Yu Guan^{2

3}, Shuiping Yin^{1

2

3}, Jun Xiao⁷, Song Xue⁸, Chaozhao Liang^{1

2

3}

Affiliations

¹ Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
² Institute of Urology, Anhui Medical University, Hefei, Anhui, China.
³ Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, Anhui, China.
⁴ Department of Oncology, Hospital of Anhui Medical University, Hefei, Anhui, China.
⁵ Department of Oncology, Anhui Public Health Clinical Center, Hefei, China.
⁶ Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁷ Department of Urology, The First Affiliated Hospital of University of Science and Technology of China (USTC), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
⁸ Department of Urology, General Hospital of Eastern Theater Command, Nanjing, China.

Abstract

Objectives: Our aim was to describe the molecular characteristics of Renal Cell Carcinoma (RCC) and develop a small panel of RCC-associated genes from a large panel of cancer-related genes.

Materials and methods: Clinical data of 55 patients with RCC diagnosed in four hospitals from September 2021 to August 2022 were collected. Among the 55 patients, 38 were diagnosed with clear cell RCC (ccRCC), and the other 17 were diagnosed with non-clear cell RCC (nccRCC), including 10 cases of papillary renal cell carcinoma, 2 cases of hereditary leiomyomatosis and RCC syndrome (HLRCC), 1 eosinophilic papillary RCC, 1 tubular cystic carcinoma, 1 TFE3 gene fusion RCC, and 2 RCC with sarcomatoid differentiation. For each patient, 1123 cancer-related genes and 79 RCC-associated genes were analyzed.

Results: The most frequent mutations in a large panel of 1123 cancer-related genes in the overall population of RCC patients were VHL (51%), PBRM1 (35%), BAP1 (16%), KMT2D (15%), PTPRD (15%), and SETD2 (15%). For ccRCC patients, mutations in VHL, PBRM1, BAP1, and SERD2 can reach 74%, 50%, 24%, and 18%, respectively, while for nccRCC patients, the most frequent mutation was FH (29%), MLH3 (24%), ARID1A (18%), KMT2D (18%), and CREBBP (18%). The germline mutation rate in all 55 patients reached 12.7% (five with FH, one with ATM, and one with RAD50). The small panel containing only 79 RCC-associated genes demonstrated that mutations of VHL, PBRM1, BAP1, and SETD2 in ccRCC patients were 74%, 50%, 24%, and 18% respectively, while for the nccRCC cohort, the most frequent mutations were FH (29%), ARID1A (18%), ATM (12%), MSH6 (12%), BRAF (12%), and KRAS (12%). For ccRCC patients, the spectrum of mutations by large and small panels was almost the same, while for nccRCC patients, the mutation spectrum showed some differences. Even though the most frequent mutations (FH and ARID1A) in nccRCC were both demonstrated by large panels and small panels, other less frequent mutations such as MLH3, KMT2D, and CREBBP were not shown by the small panel.

Conclusion: Our study revealed that nccRCC is more heterogeneous than ccRCC. For nccRCC patients, the small panel shows a more clear profile of genetic characteristics by replacing MLH3, KMT2D, and CREBBP with ATM, MSH6, BRAF, and KRAS, which may help predict prognosis and make clinical decisions.

Keywords: FH; VHL; clear cell renal cell carcinoma (ccRCC); mutation; non-clear cell renal cell carcinoma (nccRCC); renal cell carcinoma (RCC).

Grants and funding

This study was supported by the Clinical Research Special Fund of Wu Jieping Medical Foundation(320.6750.2021-04-05), and the National Natural Science Foundation of China (82102788).