Education & Certifications
B.S., Stanford University, Biomedical Computation (2021)
Spontaneous cell fusions as a mechanism of parasexual recombination in tumour cell populations
NATURE ECOLOGY & EVOLUTION
2021; 5 (3): 379–91
The initiation and progression of cancers reflect the underlying process of somatic evolution, in which the diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack access to (para)sexual recombination-a key diversification mechanism throughout all strata of life. On the basis of observations of spontaneous fusions involving cancer cells, the reported genetic instability of polypoid cells and the precedence of fusion-mediated parasexual recombination in fungi, we asked whether cell fusions between genetically distinct cancer cells could produce parasexual recombination. Using differentially labelled tumour cells, we found evidence of low-frequency, spontaneous cell fusions between carcinoma cells in multiple cell line models of breast cancer both in vitro and in vivo. While some hybrids remained polyploid, many displayed partial ploidy reduction, generating diverse progeny with heterogeneous inheritance of parental alleles, indicative of partial recombination. Hybrid cells also displayed elevated levels of phenotypic plasticity, which may further amplify the impact of cell fusions on the diversification of phenotypic traits. Using mathematical modelling, we demonstrated that the observed rates of spontaneous somatic cell fusions may enable populations of tumour cells to amplify clonal heterogeneity, thus facilitating the exploration of larger areas of the adaptive landscape (relative to strictly asexual populations), which may substantially accelerate a tumour's ability to adapt to new selective pressures.
View details for DOI 10.1038/s41559-020-01367-y
View details for Web of Science ID 000608672700001
View details for PubMedID 33462489
Optical biopsy of penile cancer with in vivo confocal laser endomicroscopy.
Surgical management of penile cancer depends on accurate margin assessment and staging. Advanced optical imaging technologies may improve penile biopsy and organ-sparing treatment. We evaluated the feasibility of confocal laser endomicroscopy for intraoperative assessment of benign and malignant penile tissue.With institutional review board approval, 11 patients were recruited, 9 with suspected penile cancer, and 2 healthy controls. Confocal laser endomicroscopy using a 2.6-mm fiber-optic probe was performed at 1 or 2 procedures on all subjects, for 13 imaging procedures. Fluorescein was administered intravenously approximately 3 minutes prior to imaging for contrast. Video sequences from in vivo (n = 12) and ex vivo (n = 6) imaging were obtained of normal glans, suspicious lesions, and surgical margins. Images were processed, annotated, characterized, and correlated with standard hematoxylin and eosin histopathology.No adverse events related to imaging were reported. Distinguishing features of benign and malignant penile tissue could be identified by confocal laser endomicroscopy. Normal skin had cells of uniform size and shape, with distinct cytoplasmic membranes consistent with squamous epithelium. Malignant lesions were characterized by disorganized, crowded cells of various size and shape, lack of distinct cytoplasmic membranes, and hazy, moth-eaten appearance. The transition from normal to abnormal squamous epithelium could be identified.We report the initial feasibility of intraoperative confocal laser endomicroscopy for penile cancer optical biopsy. Pending further evaluation, confocal laser endomicroscopy could serve as an adjunct or replacement to conventional frozen section pathology for management of penile cancer.
View details for DOI 10.1016/j.urolonc.2019.08.018
View details for PubMedID 31537485