Purpose Neuroblastoma (NB) is a heterogeneous tumor arising from sympathetic tissues. The impact of primary tumor site in influencing the heterogeneity of NB remains unclear. Patients and Methods Children younger than age 21 years diagnosed with NB or ganglioneuroblastoma between 1990 and 2002 and with known primary site were identified from the International Neuroblastoma Risk Group database. Data were compared between sites with respect to clinical and biologic features, as well as event-free survival (EFS) and overall survival (OS). Results Among 8,369 children, 47% had adrenal tumors. All evaluated clinical and biologic variables differed statistically between primary sites. The features that were > 10% discrepant between sites were stage 4 disease, MYCN amplification, elevated ferritin, elevated lactate dehydrogenase, and segmental chromosomal aberrations, all of which were more frequent in adrenal versus nonadrenal tumors (P < .001). Adrenal tumors were more likely than nonadrenal tumors (adjusted odds ratio, 2.09; 95% CI, 1.67 to 2.63; P < .001) and thoracic tumors were less likely than nonthoracic tumors (adjusted odds ratio, 0.20; 95% CI, 0.11 to 0.39; P < .001) to have MYCN amplification after controlling for age, stage, and histologic grade. EFS and OS differed significantly according to the primary site (P < .001 for both comparisons). After controlling for age, MYCN status, and stage, patients with adrenal tumors had higher risk for events (hazard ratio, 1.13 compared with nonadrenal tumors; 95% CI, 1.03 to 1.23; P = .008), and patients with thoracic tumors had lower risk for events (HR, 0.79 compared with nonthoracic; 95% CI, 0.67 to 0.92; P = .003). Conclusion Clinical and biologic features show important differences by NB primary site, with adrenal and thoracic sites associated with inferior and superior survival, respectively. Future studies will need to investigate the biologic origin of these differences.

NGS assays agnostic of primary tumour sequencing results detect ctDNA in half of the plasma samples from patients with newly diagnosed EWS and osteosarcoma. Detectable ctDNA is associated with inferior outcomes.

The deleterious effects of hybridization are a serious concern for the conservation and management of species, particularly when populations mix as a result of human activity. Outbreeding depression is the typical result observed in early-generation interpopulation hybrids of Tigriopus californicus. We examined both controlled crosses and long-term, freely-mating, experimental hybrid populations composed of southern California populations Royal Palms (RP) and San Diego (SD). Controlled crosses included parentals plus all reciprocal F1, F2, F3 and backcross cohorts, and only F2 cohorts showed significant declines in fitness compared to midparent values, indicating recovery in the F3. For long-term studies, four treatment groups were initiated: 100% RP, 100% SD, 50% RP: 50% SD, and 80% RP: 20% SD. Replicates were surveyed at 3-month intervals for morphometric, census and fitness measures. Fitness of hybrid treatments showed declines relative to midparent values followed by rapid recovery, with two hybrid replicates ultimately showing higher fitness than parentals at the final 15-month time-point (up to 20 generations). In contrast, both males and females in hybrid treatments were larger than the midparent for several morphometric characters at the first time-point, and smaller than the midparent at the final time-point, indicating a possible tradeoff between fitness and body size. Microsatellites for a subset of samples revealed extensive introgression in hybrid treatments. This adds to previous evidence that hybrid breakdown in early generations may be a temporary phenomenon followed by the persistence of highly fit recombinant genotypes.