RESUMEN
Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ cell tracing approaches with spatiotemporally controlled oncogene activation and tumor suppressor inhibition to unveil the processes underlying oral epithelial progenitor cell reprogramming into cancer stem cells (CSCs) at single cell resolution. This revealed the rapid emergence of a distinct stem-like cell state, defined by aberrant proliferative, hypoxic, squamous differentiation, and partial epithelial to mesenchymal (pEMT) invasive gene programs. Interestingly, CSCs harbor limited cell autonomous invasive capacity, but instead recruit myeloid cells to remodel the basement membrane and ultimately initiate tumor invasion. CSC transcriptional programs are conserved in human carcinomas and associated with poor patient survival. These findings illuminate the process of cancer initiation at single cell resolution, thus identifying candidate targets for early cancer detection and prevention.
RESUMEN
Tumor initiation represents the initial step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Most studies investigating cancer-driving mechanisms in solid tumors rely on analyses of established malignant lesions, and thus cannot directly capture processes underlying the reprogramming of normal progenitor cells into cancer cells. Here, using spatiotemporally controlled oncogene expression in a genetically engineered system we demonstrate that concomitant YAP activation and HPV E6-E7 -mediated inhibition of tumor suppressive pathways is sufficient to rapidly reprogram oral epithelial progenitor cells (OEPCs) into cancer stem cells (CSCs). Single cell analyses of these nascent CSCs revealed hallmark transcriptional programs driving tumor initiation. Importantly, these CSC-enriched expression signatures distinguish normal tissue from malignant head and neck tumors and are associated with poor patient survival. Elucidating mechanisms underlying OEPC to CSC reprogramming may offer new insights to halt the conversion of premalignant cells into invasive carcinoma. HIGHLIGHTS: YAP and HPV E6-E7 reprogram oral epithelial progenitor cells into cancer stem cells. Single cell analyses reveal the transcriptional architecture of tumor initiation.CSC transcriptional programs distinguish normal tissue from carcinoma.CSC signatures are associated with poor head and neck cancer survival.
RESUMEN
Linear dermatoses are fascinating entities that likely reflect embryologically derived cutaneous mosaicism, even when they occur after childhood. Adult blaschkitis is a rare, relapsing inflammatory dermatitis that most often presents in middle age. It presents clinically as a pruritic eruption of linear papules, vesicles and plaques, and is most commonly found to have features of spongiotic dermatitis on pathology. However, the clinical and histopathologic presentation of lichen striatus in adults may be similar to those of adult blaschkitis. A case in which 'blaschkitis' was suspected clinically is presented, in which the biopsy showed non-characteristic microscopic features resembling erythema multiforme--a finding rarely reported in the literature to date. We present this case and a brief review of the most commonly acquired linear eruptions following Blaschko's lines with the goal of expanding the histopathologic findings that may be encountered in adult blaschkitis. Moreover, the clinical and histopathologic overlap between the entities of blaschkitis and lichen striatus is explored, acknowledging that these entities may exist on a clinicopathologic spectrum. In the diagnosis of linear eruptions, clinicopathologic correlation is important for arriving at an accurate final diagnosis.
