The Landscape of Whole-genome Alterations and Pathologic Features in Genitourinary Malignancies: An Analysis of the Cancer Genome Atlas.
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.
['Ball|Mark W|MW|', 'Gorin|Michael A|MA|', 'Drake|Charles G|CG|', 'Hammers|Hans J|HJ|', 'Allaf|Mohamad E|ME|']
D000306:Adrenal Cortex Neoplasms D056915:DNA Copy Number Variations D018572:Disease-Free Survival D005260:Female D055106:Genome-Wide Association Study D006801:Humans D007680:Kidney Neoplasms D008297:Male D009154:Mutation D060787:Neoplasm Grading D001749:Urinary Bladder Neoplasms
Malignancy Genomics Mutations Bladder cancer Copy number alteration Kidney cancer Prostate cancer