The Landscape of Whole-genome Alterations and Pathologic Features in Genitourinary Malignancies

An Analysis of the Cancer Genome Atlas

Mark W. Ball, Michael Gorin, Charles G. Drake, Hans J. Hammers, Mohamad E Allaf

Research output: Contribution to journalArticle

Abstract

Background: The accumulation of somatic genetic alterations drives carcinogenesis. Little is known, however, about how the level of genetic alteration across an entire cancer genome affects tumor grade, stage or survival. Objective: To investigate the influence of somatic mutation count (MC) and copy number variation (CNV) on pathologic and oncologic outcomes in patients with genitourinary malignancies in The Cancer Genome Atlas (TCGA). Design, setting, and participants: TCGA data sets for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), chromophobe renal cell carcinoma (RCC; KICH), clear cell RCC (KIRC), papillary RCC (KIRP), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and testis germ cell tumor (TGCT) were accessed via cBioportal. Outcome measurements and statistical analysis: Median MC and CNV were compared among and within each tumor type. Patients were stratified by grade and stage, and differences in MC and CNV were compared. Correlation of MC and CNV with overall survival (OS) and recurrence-free survival (RFS) was analyzed when these data were available. Results and limitations: Among the tumor types analyzed, BLCA had the highest MC at 167, followed by ACC (89), KIRP (71), TGCT (55), KIRC (45), PRAD (34), PCPG (14), and KICH (12). The tumor type with the highest fraction of the genome with CNV was KICH (0.94), followed by ACC (0.58), TGCT (0.41), BLCA (0.29), KIRP (0.15), PCPG (0.13), KIRC (0.12), and PRAD (0.06). MC was associated with higher T stage in ACC, N stage in KIRC, M stage in ACC, grade in BLCA, and primary Gleason score in PRAD, and was associated with OS and RFS in KICH. CNV was associated with higher N stage in PRAD, grade in KIRC, and Gleason grade in PRAD. In addition, higher CNV was independently associated with inferior RFS for KIRC, as well as inferior OS and RFS for KIRP. Conclusions: MC and CNV vary greatly among tumor types. Patient summary: Cancers with higher levels of genomic alterations are associated with worse pathologic features and survival. The degree of genomic alterations could serve as a useful marker of disease aggressiveness. In this study of eight urologic malignancies, there was correlation between the degree of genomic alteration and pathologic aggressiveness or survival outcomes. As genomic data become more available, the degree of genomic alterations may be useful as a biomarker of biologic aggressiveness.

Original languageEnglish (US)
JournalEuropean Urology Focus
DOIs
StateAccepted/In press - 2017

Fingerprint

Atlases
Genome
Adrenocortical Carcinoma
Survival
Prostate
Adenocarcinoma
Mutation
Neoplasms
Paraganglioma
Germ Cell and Embryonal Neoplasms
Pheochromocytoma
Carcinoma
Testis
Recurrence
Urinary Bladder
Neoplasm Grading
Renal Cell Carcinoma
Urinary Bladder Neoplasms
Carcinogenesis
Biomarkers

Keywords

  • Bladder cancer
  • Copy number alteration
  • Genomics
  • Kidney cancer
  • Malignancy
  • Mutations
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

Cite this

@article{c2e7043bbcec4628a74991d715dde008,
title = "The Landscape of Whole-genome Alterations and Pathologic Features in Genitourinary Malignancies: An Analysis of the Cancer Genome Atlas",
abstract = "Background: The accumulation of somatic genetic alterations drives carcinogenesis. Little is known, however, about how the level of genetic alteration across an entire cancer genome affects tumor grade, stage or survival. Objective: To investigate the influence of somatic mutation count (MC) and copy number variation (CNV) on pathologic and oncologic outcomes in patients with genitourinary malignancies in The Cancer Genome Atlas (TCGA). Design, setting, and participants: TCGA data sets for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), chromophobe renal cell carcinoma (RCC; KICH), clear cell RCC (KIRC), papillary RCC (KIRP), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and testis germ cell tumor (TGCT) were accessed via cBioportal. Outcome measurements and statistical analysis: Median MC and CNV were compared among and within each tumor type. Patients were stratified by grade and stage, and differences in MC and CNV were compared. Correlation of MC and CNV with overall survival (OS) and recurrence-free survival (RFS) was analyzed when these data were available. Results and limitations: Among the tumor types analyzed, BLCA had the highest MC at 167, followed by ACC (89), KIRP (71), TGCT (55), KIRC (45), PRAD (34), PCPG (14), and KICH (12). The tumor type with the highest fraction of the genome with CNV was KICH (0.94), followed by ACC (0.58), TGCT (0.41), BLCA (0.29), KIRP (0.15), PCPG (0.13), KIRC (0.12), and PRAD (0.06). MC was associated with higher T stage in ACC, N stage in KIRC, M stage in ACC, grade in BLCA, and primary Gleason score in PRAD, and was associated with OS and RFS in KICH. CNV was associated with higher N stage in PRAD, grade in KIRC, and Gleason grade in PRAD. In addition, higher CNV was independently associated with inferior RFS for KIRC, as well as inferior OS and RFS for KIRP. Conclusions: MC and CNV vary greatly among tumor types. Patient summary: Cancers with higher levels of genomic alterations are associated with worse pathologic features and survival. The degree of genomic alterations could serve as a useful marker of disease aggressiveness. In this study of eight urologic malignancies, there was correlation between the degree of genomic alteration and pathologic aggressiveness or survival outcomes. As genomic data become more available, the degree of genomic alterations may be useful as a biomarker of biologic aggressiveness.",
keywords = "Bladder cancer, Copy number alteration, Genomics, Kidney cancer, Malignancy, Mutations, Prostate cancer",
author = "Ball, {Mark W.} and Michael Gorin and Drake, {Charles G.} and Hammers, {Hans J.} and Allaf, {Mohamad E}",
year = "2017",
doi = "10.1016/j.euf.2017.01.007",
language = "English (US)",
journal = "European Urology Focus",
issn = "2405-4569",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - The Landscape of Whole-genome Alterations and Pathologic Features in Genitourinary Malignancies

T2 - An Analysis of the Cancer Genome Atlas

AU - Ball, Mark W.

AU - Gorin, Michael

AU - Drake, Charles G.

AU - Hammers, Hans J.

AU - Allaf, Mohamad E

PY - 2017

Y1 - 2017

N2 - Background: The accumulation of somatic genetic alterations drives carcinogenesis. Little is known, however, about how the level of genetic alteration across an entire cancer genome affects tumor grade, stage or survival. Objective: To investigate the influence of somatic mutation count (MC) and copy number variation (CNV) on pathologic and oncologic outcomes in patients with genitourinary malignancies in The Cancer Genome Atlas (TCGA). Design, setting, and participants: TCGA data sets for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), chromophobe renal cell carcinoma (RCC; KICH), clear cell RCC (KIRC), papillary RCC (KIRP), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and testis germ cell tumor (TGCT) were accessed via cBioportal. Outcome measurements and statistical analysis: Median MC and CNV were compared among and within each tumor type. Patients were stratified by grade and stage, and differences in MC and CNV were compared. Correlation of MC and CNV with overall survival (OS) and recurrence-free survival (RFS) was analyzed when these data were available. Results and limitations: Among the tumor types analyzed, BLCA had the highest MC at 167, followed by ACC (89), KIRP (71), TGCT (55), KIRC (45), PRAD (34), PCPG (14), and KICH (12). The tumor type with the highest fraction of the genome with CNV was KICH (0.94), followed by ACC (0.58), TGCT (0.41), BLCA (0.29), KIRP (0.15), PCPG (0.13), KIRC (0.12), and PRAD (0.06). MC was associated with higher T stage in ACC, N stage in KIRC, M stage in ACC, grade in BLCA, and primary Gleason score in PRAD, and was associated with OS and RFS in KICH. CNV was associated with higher N stage in PRAD, grade in KIRC, and Gleason grade in PRAD. In addition, higher CNV was independently associated with inferior RFS for KIRC, as well as inferior OS and RFS for KIRP. Conclusions: MC and CNV vary greatly among tumor types. Patient summary: Cancers with higher levels of genomic alterations are associated with worse pathologic features and survival. The degree of genomic alterations could serve as a useful marker of disease aggressiveness. In this study of eight urologic malignancies, there was correlation between the degree of genomic alteration and pathologic aggressiveness or survival outcomes. As genomic data become more available, the degree of genomic alterations may be useful as a biomarker of biologic aggressiveness.

AB - Background: The accumulation of somatic genetic alterations drives carcinogenesis. Little is known, however, about how the level of genetic alteration across an entire cancer genome affects tumor grade, stage or survival. Objective: To investigate the influence of somatic mutation count (MC) and copy number variation (CNV) on pathologic and oncologic outcomes in patients with genitourinary malignancies in The Cancer Genome Atlas (TCGA). Design, setting, and participants: TCGA data sets for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), chromophobe renal cell carcinoma (RCC; KICH), clear cell RCC (KIRC), papillary RCC (KIRP), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and testis germ cell tumor (TGCT) were accessed via cBioportal. Outcome measurements and statistical analysis: Median MC and CNV were compared among and within each tumor type. Patients were stratified by grade and stage, and differences in MC and CNV were compared. Correlation of MC and CNV with overall survival (OS) and recurrence-free survival (RFS) was analyzed when these data were available. Results and limitations: Among the tumor types analyzed, BLCA had the highest MC at 167, followed by ACC (89), KIRP (71), TGCT (55), KIRC (45), PRAD (34), PCPG (14), and KICH (12). The tumor type with the highest fraction of the genome with CNV was KICH (0.94), followed by ACC (0.58), TGCT (0.41), BLCA (0.29), KIRP (0.15), PCPG (0.13), KIRC (0.12), and PRAD (0.06). MC was associated with higher T stage in ACC, N stage in KIRC, M stage in ACC, grade in BLCA, and primary Gleason score in PRAD, and was associated with OS and RFS in KICH. CNV was associated with higher N stage in PRAD, grade in KIRC, and Gleason grade in PRAD. In addition, higher CNV was independently associated with inferior RFS for KIRC, as well as inferior OS and RFS for KIRP. Conclusions: MC and CNV vary greatly among tumor types. Patient summary: Cancers with higher levels of genomic alterations are associated with worse pathologic features and survival. The degree of genomic alterations could serve as a useful marker of disease aggressiveness. In this study of eight urologic malignancies, there was correlation between the degree of genomic alteration and pathologic aggressiveness or survival outcomes. As genomic data become more available, the degree of genomic alterations may be useful as a biomarker of biologic aggressiveness.

KW - Bladder cancer

KW - Copy number alteration

KW - Genomics

KW - Kidney cancer

KW - Malignancy

KW - Mutations

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85011887530&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85011887530&partnerID=8YFLogxK

U2 - 10.1016/j.euf.2017.01.007

DO - 10.1016/j.euf.2017.01.007

M3 - Article

JO - European Urology Focus

JF - European Urology Focus

SN - 2405-4569

ER -