Next-Generation Sequencing to Detect Deletion of RB1 and ERBB4 Genes in Chromophobe Renal Cell Carcinoma: A Potential Role in Distinguishing Chromophobe Renal Cell Carcinoma from Renal Oncocytoma

Qingqing Liu, Kristine M. Cornejo, Liang Cheng, Lloyd Hutchinson, Mingsheng Wang, Shaobo Zhang, Keith Tomaszewicz, Ediz F. Cosar, Bruce A. Woda, Zhong Jiang

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Abstract

Overlapping morphologic, immunohistochemical, and ultrastructural features make it difficult to diagnose chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). Because ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to identify genetic markers that distinguish ChRCC from RO by using next-generation sequencing (NGS). NGS for hotspot mutations or gene copy number changes was performed on 12 renal neoplasms, including seven ChRCC and five RO cases. Matched normal tissues from the same patients were used to exclude germline variants. Rare hotspot mutations were found in cancer-critical genes (TP53 and PIK3CA) in ChRCC but not RO. The NGS gene copy number analysis revealed multiple abnormalities. The two most common deletions were tumor-suppressor genes RB1 and ERBB4 in ChRCC but not RO. Fluorescence in situ hybridization was performed on 65 cases (ChRCC, n = 33; RO, n = 32) to verify hemizygous deletion of RB1 (17/33, 52%) or ERBB4 (11/33, 33%) in ChRCC, but not in RO (0/32, 0%). In total, ChRCCs (23/33, 70%) carry either a hemizygous deletion of RB1 or ERBB4. The combined use of RB1 and ERBB4 fluorescence in situ hybridization to detect deletion of these genes may offer a highly sensitive and specific assay to distinguish ChRCC from RO.

Original languageEnglish (US)
Pages (from-to)846-852
Number of pages7
JournalAmerican Journal of Pathology
Volume188
Issue number4
DOIs
StatePublished - Apr 1 2018

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Renal Cell Carcinoma
Genes
Gene Dosage
Fluorescence In Situ Hybridization
Multiple Abnormalities
Renal oncocytoma
Mutation
Kidney Neoplasms
Neoplasm Genes
Gene Deletion
Tumor Suppressor Genes
Genetic Markers
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Next-Generation Sequencing to Detect Deletion of RB1 and ERBB4 Genes in Chromophobe Renal Cell Carcinoma : A Potential Role in Distinguishing Chromophobe Renal Cell Carcinoma from Renal Oncocytoma. / Liu, Qingqing; Cornejo, Kristine M.; Cheng, Liang; Hutchinson, Lloyd; Wang, Mingsheng; Zhang, Shaobo; Tomaszewicz, Keith; Cosar, Ediz F.; Woda, Bruce A.; Jiang, Zhong.

In: American Journal of Pathology, Vol. 188, No. 4, 01.04.2018, p. 846-852.

Research output: Contribution to journalArticle

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abstract = "Overlapping morphologic, immunohistochemical, and ultrastructural features make it difficult to diagnose chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). Because ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to identify genetic markers that distinguish ChRCC from RO by using next-generation sequencing (NGS). NGS for hotspot mutations or gene copy number changes was performed on 12 renal neoplasms, including seven ChRCC and five RO cases. Matched normal tissues from the same patients were used to exclude germline variants. Rare hotspot mutations were found in cancer-critical genes (TP53 and PIK3CA) in ChRCC but not RO. The NGS gene copy number analysis revealed multiple abnormalities. The two most common deletions were tumor-suppressor genes RB1 and ERBB4 in ChRCC but not RO. Fluorescence in situ hybridization was performed on 65 cases (ChRCC, n = 33; RO, n = 32) to verify hemizygous deletion of RB1 (17/33, 52{\%}) or ERBB4 (11/33, 33{\%}) in ChRCC, but not in RO (0/32, 0{\%}). In total, ChRCCs (23/33, 70{\%}) carry either a hemizygous deletion of RB1 or ERBB4. The combined use of RB1 and ERBB4 fluorescence in situ hybridization to detect deletion of these genes may offer a highly sensitive and specific assay to distinguish ChRCC from RO.",
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AU - Liu, Qingqing

AU - Cornejo, Kristine M.

AU - Cheng, Liang

AU - Hutchinson, Lloyd

AU - Wang, Mingsheng

AU - Zhang, Shaobo

AU - Tomaszewicz, Keith

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