Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing for a detailed description of the somatic mutational landscape of ccRCC. We identify candidate driver genes, which as well as emphasising the major role of epigenetic regulation in ccRCC highlight additional biological pathways extending opportunities for therapeutic interventions. Genomic characterisation identified patients with divergent clinical outcome; higher number of structural copy number alterations associated with poorer prognosis, whereas VHL mutations were independently associated with a better prognosis. The observations that higher T-cell infiltration is associated with better overall survival and that genetically predicted immune evasion is not common supports the rationale for immunotherapy. These findings should inform personalised surveillance and treatment strategies for ccRCC patients.

Genetic landscape of interval and screen detected breast cancer.

Interval breast cancers (IBCs) are cancers diagnosed between screening episodes. Understanding the biological differences between IBCs and screen-detected breast-cancers (SDBCs) has the potential to improve mammographic screening and patient management. We analysed and compared the genomic landscape of 288 IBCs and 473 SDBCs by whole genome sequencing of paired tumour-normal patient samples collected as part of the UK 100,000 Genomes Project. Compared to SDBCs, IBCs were more likely to be lobular, higher grade, and triple negative. A more aggressive clinical phenotype was reflected in IBCs displaying features of genomic instability including a higher mutation rate and number of chromosomal structural abnormalities, defective homologous recombination and TP53 mutations. We did not however, find evidence to indicate that IBCs are associated with a significantly different immune response. While IBCs do not represent a unique molecular class of invasive breast cancer they exhibit a more aggressive phenotype, which is likely to be a consequence of the timing of tumour initiation. This information is relevant both with respect to treatment as well as informing the screening interval for mammography.

Do hospital factors impact readmissions and mortality after colorectal resections at minority-serving hospitals?

BACKGROUND: Minority-serving hospitals have greater readmission rates after operative procedures including colectomy; however, little is known about the contribution of hospital factors to readmission risk and mortality in this setting. This study evaluated the impact of hospital factors on readmissions and inpatient mortality after colorectal resections at minority-serving hospitals in the context of patient- and procedure-related factors. METHODS: More than 168,000 patients who underwent colorectal resections in 374 California hospitals (2004-2011) were analyzed using the State Inpatient Database and American Hospital Association Hospital Survey data. Sequential logistic regression analyses were performed to determine the associations between minority-serving hospital status and 30-day, 90-day, and repeated readmissions. RESULTS: Thirty-day, 90-day, and repeated readmission rates were 11.2%, 16.9%, and 2.9%, respectively. Odds for 30-day, 90-day, and repeated readmissions after colorectal resections were 19%, 20%, and 38% more likely at minority-serving hospitals versus non-minority-serving hospitals, respectively (P < .01), after controlling for age, sex, comorbidities, year, and procedure type. Patient factors accounted for up to 65% of the observed increase in odds for readmission at minority-serving hospitals while hospital-level factors contributed roughly 40%. Inpatient mortality was significantly greater at minority-serving hospitals versus non-minority-serving hospitals (4.9% vs 3.8%; P < .001). Risk factors significantly associated with readmissions and inpatient mortality included Medicaid/Medicare primary insurance, emergent operation, and ostomy creation. Low procedure volume was significantly associated with increased odds for inpatient mortality. CONCLUSION: Patient-level factors seemed to dominate the increased readmission risk after colorectal resections at minority-serving hospitals while hospital factors were less contributory. These findings need to be further validated to shape quality improvement interventions to decrease readmissions.