Genetic Evidence for Early Peritoneal Spreading in Pelvic High-Grade Serous Cancer.

BACKGROUND: Most pelvic high-grade serous (HGS) carcinomas have been proposed to arise from tubal primaries that progress rapidly to advanced disease. However, the temporal sequence of ovarian and peritoneal metastases is not well characterized. METHODS: To establish the sequence of metastases, phylogenetic relationships among the ovarian and peritoneal carcinomas were determined from single-nucleotide variations (SNVs) in nine tumor regions from each patient with pelvic HGS carcinomas. Somatic SNVs from each tumor sample were used to reconstruct phylogenies of samples from each patient. Variant allele frequencies were used to reconstruct subclone phylogenies in each tumor sample. RESULTS: We show that pelvic HGS carcinomas are highly heterogeneous, only sharing less than 4% of somatic SNVs among all nine carcinoma implants in one patient. TP53 mutations are found in all nine carcinoma implants in each patient. The phylogenetic analyses reveal that peritoneal metastases arose from early branching events that preceded branching events for ovarian carcinomas in some patients. Finally, subclone phylogenies indicate the presence of multiple subclones at each tumor implant and early tumor clones in peritoneal implants. CONCLUSION: The genetic evidence that peritoneal implants arose before or concurrently with ovarian implants is consistent with the emerging concept of the extra-ovarian origin of pelvic HGS cancer. Our results challenge the concept of stepwise spatial progression from the fallopian primary to ovarian carcinomas to peritoneal dissemination and suggest an alternative progression model where peritoneal spreading of early clones occurs before or in parallel with ovarian metastases.

A revised classification of the Icteridae (Aves) based on DNA sequence data.

The higher-level classification of the New World blackbirds (Icteridae; Aves) has remained relatively stable for nearly a half-century, with most currently used classifications (e.g. Sibley & Monroe 1990; Jaramillo & Burke 1999; Fraga 2011; Remsen et al. 2015) following Blake's (1968) delimitation and sequence of genera in the Peters Check-list of Birds of the World series. Early molecular studies (e.g., Lanyon 1992, 1994; Johnson & Lanyon 1999; Price & Lanyon 2002; Cadena et al. 2004) produced only minor modifications.

A comprehensive species-level molecular phylogeny of the New World blackbirds (Icteridae).

The New World blackbirds (Icteridae) are among the best known songbirds, serving as a model clade in comparative studies of morphological, ecological, and behavioral trait evolution. Despite wide interest in the group, as yet no analysis of blackbird relationships has achieved comprehensive species-level sampling or found robust support for most intergeneric relationships. Using mitochondrial gene sequences from all ∼108 currently recognized species and six additional distinct lineages, together with strategic sampling of four nuclear loci and whole mitochondrial genomes, we were able to resolve most relationships with high confidence. Our phylogeny is consistent with the strongly-supported results of past studies, but it also contains many novel inferences of relationship, including unexpected placement of some newly-sampled taxa, resolution of relationships among major clades within Icteridae, and resolution of genus-level relationships within the largest of those clades, the grackles and allies. We suggest taxonomic revisions based on our results, including restoration of Cacicus melanicterus to the monotypic Cassiculus, merging the monotypic Ocyalus and Clypicterus into Cacicus, restoration of Dives atroviolaceus to the monotypic Ptiloxena, and naming Curaeus forbesi to a new genus, Anumara. Our hypothesis of blackbird phylogeny provides a foundation for ongoing and future evolutionary analyses of the group.

Empirical evaluation of partitioning schemes for phylogenetic analyses of mitogenomic data: an avian case study.

Whole mitochondrial genome sequences have been used in studies of animal phylogeny for two decades, and current technologies make them ever more available, but methods for their analysis are lagging and best practices have not been established. Most studies ignore variation in base composition and evolutionary rate within the mitogenome that can bias phylogenetic inference, or attempt to avoid it by excluding parts of the mitogenome from analysis. In contrast, partitioned analyses accommodate heterogeneity, without discarding data, by applying separate evolutionary models to differing portions of the mitogenome. To facilitate use of complete mitogenomic sequences in phylogenetics, we (1) suggest a set of categories for dividing mitogenomic datasets into subsets, (2) explore differences in evolutionary dynamics among those subsets, and (3) apply a method for combining data subsets with similar properties to produce effective and efficient partitioning schemes. We demonstrate these procedures with a case study, using the mitogenomes of species in the grackles and allies clade of New World blackbirds (Icteridae). We found that the most useful categories for partitioning were codon position, RNA secondary structure pairing, and the coding/noncoding distinction, and that a scheme with nine data groups outperformed all of the more complex alternatives (up to 44 data groups) that we tested. As hoped, we found that analyses using whole mitogenomic sequences yielded much better-resolved and more strongly-supported hypotheses of the phylogenetic history of that locus than did a conventional 2-kilobase sample (i.e. sequences of the cytochrome b and ND2 genes). Mitogenomes have much untapped potential for phylogenetics, especially of birds, a taxon for which they have been little exploited except in investigations of ordinal-level relationships.