The classification of pediatric and young adult renal cell carcinomas registered on the children's oncology group (COG) protocol AREN03B2 after focused genetic testing

Mariana M. Cajaiba*, Lisa M. Dyer, James I. Geller, Lawrence J Jennings, David George, Dawn Kirschmann, Stephen M. Rohan, Nicholas G. Cost, Geetika Khanna, Elizabeth A. Mullen, Jeffrey S. Dome, Conrad V. Fernandez, Elizabeth J Perlman

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

BACKGROUND: Renal cell carcinomas (RCCs) are rare in young patients. Knowledge of their pathologic and molecular spectrum remains limited, and no prospective studies have been performed to date in this population. This study analyzes patients diagnosed with RCC who were prospectively enrolled in the AREN03B2 Children's Oncology Group (COG). The objective was to classify these tumors with the aid of focused genetic testing and to characterize their features. METHODS: All tumors registered as RCC by central review were retrospectively re-reviewed and underwent additional ancillary studies. Tumors were classified according to the 2016 World Health Organization classification system when possible. RESULTS: In total, 212 tumors were identified, and these were classified as microphthalmia transcription factor (MiT) translocation RCC (MiT-RCC) (41.5%), papillary RCC (16.5%), renal medullary carcinoma (12.3%), chromophobe RCC (6.6%), clear cell RCC (3.3%), fumarate hydratase-deficient RCC (1.4%), and succinate dehydrogenase-deficient RCC (0.5%). Other subtypes included tuberous sclerosis-associated RCC (4.2%), anaplastic lymphoma kinase (ALK)-rearranged RCC (3.8%), thyroid-like RCC (1.4%), myoepithelial carcinoma (0.9%), and unclassified (7.5%). MiT-RCCs were classified as either transcription factor E3 (TFE3) (93.2%) or EB (TFEB) (6.8%) translocations, and characterization of fusion partners was possible in most tumors. CONCLUSIONS: The current study delineates the frequency of distinct RCC subtypes in a large prospective series of young patients and contributes knowledge to the diagnostic, clinical, and genetic features of MiT-RCC, the most common subtype among this age group. The identification of rare subtypes expands the spectrum of RCC in young patients, supporting the need for a thorough diagnostic workup. These studies may aid in the introduction of specific therapies for different RCC subtypes in the future. Cancer 2018.

Original languageEnglish (US)
Pages (from-to)3381-3389
Number of pages9
JournalCancer
Volume124
Issue number16
DOIs
StatePublished - Aug 1 2018

Fingerprint

Genetic Testing
Renal Cell Carcinoma
Young Adult
Pediatrics
Microphthalmia-Associated Transcription Factor
Neoplasms
Fumarate Hydratase
Medullary Carcinoma
Tuberous Sclerosis
Succinate Dehydrogenase

Keywords

  • pediatric renal tumor
  • renal cell carcinoma
  • transcription factor E3 (TFE3) gene
  • transcription factor EB (TFEB) gene
  • translocation renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cajaiba, Mariana M. ; Dyer, Lisa M. ; Geller, James I. ; Jennings, Lawrence J ; George, David ; Kirschmann, Dawn ; Rohan, Stephen M. ; Cost, Nicholas G. ; Khanna, Geetika ; Mullen, Elizabeth A. ; Dome, Jeffrey S. ; Fernandez, Conrad V. ; Perlman, Elizabeth J. / The classification of pediatric and young adult renal cell carcinomas registered on the children's oncology group (COG) protocol AREN03B2 after focused genetic testing. In: Cancer. 2018 ; Vol. 124, No. 16. pp. 3381-3389.
@article{8806fefd39a546078d3e01b092256c94,
title = "The classification of pediatric and young adult renal cell carcinomas registered on the children's oncology group (COG) protocol AREN03B2 after focused genetic testing",
abstract = "BACKGROUND: Renal cell carcinomas (RCCs) are rare in young patients. Knowledge of their pathologic and molecular spectrum remains limited, and no prospective studies have been performed to date in this population. This study analyzes patients diagnosed with RCC who were prospectively enrolled in the AREN03B2 Children's Oncology Group (COG). The objective was to classify these tumors with the aid of focused genetic testing and to characterize their features. METHODS: All tumors registered as RCC by central review were retrospectively re-reviewed and underwent additional ancillary studies. Tumors were classified according to the 2016 World Health Organization classification system when possible. RESULTS: In total, 212 tumors were identified, and these were classified as microphthalmia transcription factor (MiT) translocation RCC (MiT-RCC) (41.5{\%}), papillary RCC (16.5{\%}), renal medullary carcinoma (12.3{\%}), chromophobe RCC (6.6{\%}), clear cell RCC (3.3{\%}), fumarate hydratase-deficient RCC (1.4{\%}), and succinate dehydrogenase-deficient RCC (0.5{\%}). Other subtypes included tuberous sclerosis-associated RCC (4.2{\%}), anaplastic lymphoma kinase (ALK)-rearranged RCC (3.8{\%}), thyroid-like RCC (1.4{\%}), myoepithelial carcinoma (0.9{\%}), and unclassified (7.5{\%}). MiT-RCCs were classified as either transcription factor E3 (TFE3) (93.2{\%}) or EB (TFEB) (6.8{\%}) translocations, and characterization of fusion partners was possible in most tumors. CONCLUSIONS: The current study delineates the frequency of distinct RCC subtypes in a large prospective series of young patients and contributes knowledge to the diagnostic, clinical, and genetic features of MiT-RCC, the most common subtype among this age group. The identification of rare subtypes expands the spectrum of RCC in young patients, supporting the need for a thorough diagnostic workup. These studies may aid in the introduction of specific therapies for different RCC subtypes in the future. Cancer 2018.",
keywords = "pediatric renal tumor, renal cell carcinoma, transcription factor E3 (TFE3) gene, transcription factor EB (TFEB) gene, translocation renal cell carcinoma",
author = "Cajaiba, {Mariana M.} and Dyer, {Lisa M.} and Geller, {James I.} and Jennings, {Lawrence J} and David George and Dawn Kirschmann and Rohan, {Stephen M.} and Cost, {Nicholas G.} and Geetika Khanna and Mullen, {Elizabeth A.} and Dome, {Jeffrey S.} and Fernandez, {Conrad V.} and Perlman, {Elizabeth J}",
year = "2018",
month = "8",
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doi = "10.1002/cncr.31578",
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Cajaiba, MM, Dyer, LM, Geller, JI, Jennings, LJ, George, D, Kirschmann, D, Rohan, SM, Cost, NG, Khanna, G, Mullen, EA, Dome, JS, Fernandez, CV & Perlman, EJ 2018, 'The classification of pediatric and young adult renal cell carcinomas registered on the children's oncology group (COG) protocol AREN03B2 after focused genetic testing', Cancer, vol. 124, no. 16, pp. 3381-3389. https://doi.org/10.1002/cncr.31578

The classification of pediatric and young adult renal cell carcinomas registered on the children's oncology group (COG) protocol AREN03B2 after focused genetic testing. / Cajaiba, Mariana M.; Dyer, Lisa M.; Geller, James I.; Jennings, Lawrence J; George, David; Kirschmann, Dawn; Rohan, Stephen M.; Cost, Nicholas G.; Khanna, Geetika; Mullen, Elizabeth A.; Dome, Jeffrey S.; Fernandez, Conrad V.; Perlman, Elizabeth J.

In: Cancer, Vol. 124, No. 16, 01.08.2018, p. 3381-3389.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The classification of pediatric and young adult renal cell carcinomas registered on the children's oncology group (COG) protocol AREN03B2 after focused genetic testing

AU - Cajaiba, Mariana M.

AU - Dyer, Lisa M.

AU - Geller, James I.

AU - Jennings, Lawrence J

AU - George, David

AU - Kirschmann, Dawn

AU - Rohan, Stephen M.

AU - Cost, Nicholas G.

AU - Khanna, Geetika

AU - Mullen, Elizabeth A.

AU - Dome, Jeffrey S.

AU - Fernandez, Conrad V.

AU - Perlman, Elizabeth J

PY - 2018/8/1

Y1 - 2018/8/1

N2 - BACKGROUND: Renal cell carcinomas (RCCs) are rare in young patients. Knowledge of their pathologic and molecular spectrum remains limited, and no prospective studies have been performed to date in this population. This study analyzes patients diagnosed with RCC who were prospectively enrolled in the AREN03B2 Children's Oncology Group (COG). The objective was to classify these tumors with the aid of focused genetic testing and to characterize their features. METHODS: All tumors registered as RCC by central review were retrospectively re-reviewed and underwent additional ancillary studies. Tumors were classified according to the 2016 World Health Organization classification system when possible. RESULTS: In total, 212 tumors were identified, and these were classified as microphthalmia transcription factor (MiT) translocation RCC (MiT-RCC) (41.5%), papillary RCC (16.5%), renal medullary carcinoma (12.3%), chromophobe RCC (6.6%), clear cell RCC (3.3%), fumarate hydratase-deficient RCC (1.4%), and succinate dehydrogenase-deficient RCC (0.5%). Other subtypes included tuberous sclerosis-associated RCC (4.2%), anaplastic lymphoma kinase (ALK)-rearranged RCC (3.8%), thyroid-like RCC (1.4%), myoepithelial carcinoma (0.9%), and unclassified (7.5%). MiT-RCCs were classified as either transcription factor E3 (TFE3) (93.2%) or EB (TFEB) (6.8%) translocations, and characterization of fusion partners was possible in most tumors. CONCLUSIONS: The current study delineates the frequency of distinct RCC subtypes in a large prospective series of young patients and contributes knowledge to the diagnostic, clinical, and genetic features of MiT-RCC, the most common subtype among this age group. The identification of rare subtypes expands the spectrum of RCC in young patients, supporting the need for a thorough diagnostic workup. These studies may aid in the introduction of specific therapies for different RCC subtypes in the future. Cancer 2018.

AB - BACKGROUND: Renal cell carcinomas (RCCs) are rare in young patients. Knowledge of their pathologic and molecular spectrum remains limited, and no prospective studies have been performed to date in this population. This study analyzes patients diagnosed with RCC who were prospectively enrolled in the AREN03B2 Children's Oncology Group (COG). The objective was to classify these tumors with the aid of focused genetic testing and to characterize their features. METHODS: All tumors registered as RCC by central review were retrospectively re-reviewed and underwent additional ancillary studies. Tumors were classified according to the 2016 World Health Organization classification system when possible. RESULTS: In total, 212 tumors were identified, and these were classified as microphthalmia transcription factor (MiT) translocation RCC (MiT-RCC) (41.5%), papillary RCC (16.5%), renal medullary carcinoma (12.3%), chromophobe RCC (6.6%), clear cell RCC (3.3%), fumarate hydratase-deficient RCC (1.4%), and succinate dehydrogenase-deficient RCC (0.5%). Other subtypes included tuberous sclerosis-associated RCC (4.2%), anaplastic lymphoma kinase (ALK)-rearranged RCC (3.8%), thyroid-like RCC (1.4%), myoepithelial carcinoma (0.9%), and unclassified (7.5%). MiT-RCCs were classified as either transcription factor E3 (TFE3) (93.2%) or EB (TFEB) (6.8%) translocations, and characterization of fusion partners was possible in most tumors. CONCLUSIONS: The current study delineates the frequency of distinct RCC subtypes in a large prospective series of young patients and contributes knowledge to the diagnostic, clinical, and genetic features of MiT-RCC, the most common subtype among this age group. The identification of rare subtypes expands the spectrum of RCC in young patients, supporting the need for a thorough diagnostic workup. These studies may aid in the introduction of specific therapies for different RCC subtypes in the future. Cancer 2018.

KW - pediatric renal tumor

KW - renal cell carcinoma

KW - transcription factor E3 (TFE3) gene

KW - transcription factor EB (TFEB) gene

KW - translocation renal cell carcinoma

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DO - 10.1002/cncr.31578

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JO - Cancer

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SN - 0008-543X

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