Preservation of truncal genomic alterations in clear cell and papillary renal cell carcinomas with sarcomatoid features: An intra- and intertumoral, multifocal fluorescence in situ hybridization analysis reveals limited genetic heterogeneity

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Abstract

Understanding tumor genomic heterogeneity may offer vital information in an age of targeted therapy for renal cell carcinoma. We sought to investigate hallmark truncal chromosomal alterations between conventional, sarcomatoid, and matched metastatic tumor foci in clear cell and papillary renal cell carcinomas. A retrospective review identified 58 cases including clear cell (CCRCC) and papillary renal cell carcinomas (PRCC). All cases contained sarcomatoid transformation. Additionally, 10 of 58 patients had matched metastatic disease available for analysis. Three separate foci of conventional and sarcomatoid morphologies were analyzed in each tumor using dual color interphase fluorescence in situ hybridization. In the CCRCC cohort, hallmark chromosome 3p deletion was identified in 71% of cases (37/52). Complete concordance of chromosomal status between intratumoral foci in sarcomatoid and conventional foci was 89% and 86%, respectively. Overall chromosome 3p status between matched conventional and sarcomatoid morphologies was identified in 98% of cases (51/52). Hallmark 3p deletion was present in 91% of CCRCC metastatic samples (10/11) and was concordant with the matched primary CCRCC tumor in 91% (10/11). In the PRCC cohort, trisomy 7 and 17 was identified in all six cases (6/6). Complete concordance between intratumoral foci of trisomy 7 and 17 was 83% (5/6). Trisomy 7 and 17 were identified in all metastatic PRCC samples with 100% concordance with the matched primary tumor. These data show the relative preservation of truncal chromosomal abnormalities between conventional and sarcomatoid morphologic as well as matched metastatic settings.

Original languageEnglish (US)
JournalMolecular Carcinogenesis
DOIs
StateAccepted/In press - 2017

Fingerprint

Genetic Heterogeneity
Fluorescence In Situ Hybridization
Renal Cell Carcinoma
Neoplasms
Chromosome Deletion
Interphase
Chromosome Aberrations
Color
Chromosomes
Chromosome 17 trisomy

Keywords

  • Differential diagnosis
  • Fluorescence in situ hybridization (FISH)
  • Kidney
  • Molecular genetics/cytogenetics
  • Precision medicine
  • Sarcomatoid renal cell carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

@article{1bfc25917bc34935978a5d59697694c9,
title = "Preservation of truncal genomic alterations in clear cell and papillary renal cell carcinomas with sarcomatoid features: An intra- and intertumoral, multifocal fluorescence in situ hybridization analysis reveals limited genetic heterogeneity",
abstract = "Understanding tumor genomic heterogeneity may offer vital information in an age of targeted therapy for renal cell carcinoma. We sought to investigate hallmark truncal chromosomal alterations between conventional, sarcomatoid, and matched metastatic tumor foci in clear cell and papillary renal cell carcinomas. A retrospective review identified 58 cases including clear cell (CCRCC) and papillary renal cell carcinomas (PRCC). All cases contained sarcomatoid transformation. Additionally, 10 of 58 patients had matched metastatic disease available for analysis. Three separate foci of conventional and sarcomatoid morphologies were analyzed in each tumor using dual color interphase fluorescence in situ hybridization. In the CCRCC cohort, hallmark chromosome 3p deletion was identified in 71{\%} of cases (37/52). Complete concordance of chromosomal status between intratumoral foci in sarcomatoid and conventional foci was 89{\%} and 86{\%}, respectively. Overall chromosome 3p status between matched conventional and sarcomatoid morphologies was identified in 98{\%} of cases (51/52). Hallmark 3p deletion was present in 91{\%} of CCRCC metastatic samples (10/11) and was concordant with the matched primary CCRCC tumor in 91{\%} (10/11). In the PRCC cohort, trisomy 7 and 17 was identified in all six cases (6/6). Complete concordance between intratumoral foci of trisomy 7 and 17 was 83{\%} (5/6). Trisomy 7 and 17 were identified in all metastatic PRCC samples with 100{\%} concordance with the matched primary tumor. These data show the relative preservation of truncal chromosomal abnormalities between conventional and sarcomatoid morphologic as well as matched metastatic settings.",
keywords = "Differential diagnosis, Fluorescence in situ hybridization (FISH), Kidney, Molecular genetics/cytogenetics, Precision medicine, Sarcomatoid renal cell carcinoma",
author = "Sanfrancesco, {Joseph M.} and John Eble and David Grignon and Mingsheng Wang and Shaobo Zhang and Chandru Sundaram and Muhammad Idrees and Roberto Pili and Erik Kouba and Liang Cheng",
year = "2017",
doi = "10.1002/mc.22699",
language = "English (US)",
journal = "Molecular Carcinogenesis",
issn = "0899-1987",
publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Preservation of truncal genomic alterations in clear cell and papillary renal cell carcinomas with sarcomatoid features

T2 - An intra- and intertumoral, multifocal fluorescence in situ hybridization analysis reveals limited genetic heterogeneity

AU - Sanfrancesco, Joseph M.

AU - Eble, John

AU - Grignon, David

AU - Wang, Mingsheng

AU - Zhang, Shaobo

AU - Sundaram, Chandru

AU - Idrees, Muhammad

AU - Pili, Roberto

AU - Kouba, Erik

AU - Cheng, Liang

PY - 2017

Y1 - 2017

N2 - Understanding tumor genomic heterogeneity may offer vital information in an age of targeted therapy for renal cell carcinoma. We sought to investigate hallmark truncal chromosomal alterations between conventional, sarcomatoid, and matched metastatic tumor foci in clear cell and papillary renal cell carcinomas. A retrospective review identified 58 cases including clear cell (CCRCC) and papillary renal cell carcinomas (PRCC). All cases contained sarcomatoid transformation. Additionally, 10 of 58 patients had matched metastatic disease available for analysis. Three separate foci of conventional and sarcomatoid morphologies were analyzed in each tumor using dual color interphase fluorescence in situ hybridization. In the CCRCC cohort, hallmark chromosome 3p deletion was identified in 71% of cases (37/52). Complete concordance of chromosomal status between intratumoral foci in sarcomatoid and conventional foci was 89% and 86%, respectively. Overall chromosome 3p status between matched conventional and sarcomatoid morphologies was identified in 98% of cases (51/52). Hallmark 3p deletion was present in 91% of CCRCC metastatic samples (10/11) and was concordant with the matched primary CCRCC tumor in 91% (10/11). In the PRCC cohort, trisomy 7 and 17 was identified in all six cases (6/6). Complete concordance between intratumoral foci of trisomy 7 and 17 was 83% (5/6). Trisomy 7 and 17 were identified in all metastatic PRCC samples with 100% concordance with the matched primary tumor. These data show the relative preservation of truncal chromosomal abnormalities between conventional and sarcomatoid morphologic as well as matched metastatic settings.

AB - Understanding tumor genomic heterogeneity may offer vital information in an age of targeted therapy for renal cell carcinoma. We sought to investigate hallmark truncal chromosomal alterations between conventional, sarcomatoid, and matched metastatic tumor foci in clear cell and papillary renal cell carcinomas. A retrospective review identified 58 cases including clear cell (CCRCC) and papillary renal cell carcinomas (PRCC). All cases contained sarcomatoid transformation. Additionally, 10 of 58 patients had matched metastatic disease available for analysis. Three separate foci of conventional and sarcomatoid morphologies were analyzed in each tumor using dual color interphase fluorescence in situ hybridization. In the CCRCC cohort, hallmark chromosome 3p deletion was identified in 71% of cases (37/52). Complete concordance of chromosomal status between intratumoral foci in sarcomatoid and conventional foci was 89% and 86%, respectively. Overall chromosome 3p status between matched conventional and sarcomatoid morphologies was identified in 98% of cases (51/52). Hallmark 3p deletion was present in 91% of CCRCC metastatic samples (10/11) and was concordant with the matched primary CCRCC tumor in 91% (10/11). In the PRCC cohort, trisomy 7 and 17 was identified in all six cases (6/6). Complete concordance between intratumoral foci of trisomy 7 and 17 was 83% (5/6). Trisomy 7 and 17 were identified in all metastatic PRCC samples with 100% concordance with the matched primary tumor. These data show the relative preservation of truncal chromosomal abnormalities between conventional and sarcomatoid morphologic as well as matched metastatic settings.

KW - Differential diagnosis

KW - Fluorescence in situ hybridization (FISH)

KW - Kidney

KW - Molecular genetics/cytogenetics

KW - Precision medicine

KW - Sarcomatoid renal cell carcinoma

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U2 - 10.1002/mc.22699

DO - 10.1002/mc.22699

M3 - Article

C2 - 28667776

AN - SCOPUS:85026774200

JO - Molecular Carcinogenesis

JF - Molecular Carcinogenesis

SN - 0899-1987

ER -