Project description:Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as “metastatic choriocarcinoma” (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of “adenocarcinoma with aberrant expression of β-hCG” and finally pathologists at our hospital, who gave the diagnosis of “poorly differentiated carcinoma with choriocarcinoma features”. Genomic profiling detected a KRAS G13R mutation and transcriptomics profiling was suggestive of lung origin. The patient was treated with carboplatin/paclitaxel/ipilimumab/nivolumab followed by consolidation radiation therapy. She had no evidence of progression to date, 13 months after the initial presentation. The molecular profiling could facilitate diagnosing of challenging cancer cases. In addition, chemoimmunotherapy and local consolidation radiation therapy may provide promising therapeutic options for patients with lung cancer exhibiting choriocarcinoma features.
Project description:The cellular origin of cervical cancers remains unclear. Revealing molecular details of transformation in this tissue has been hampered by the lack of culture systems, resembling the in vivo cervical architecture. Here we established a long-term in vitro 3D cervical organoid model derived from stem cells of human or mouse cervical tissue which recapitulates the in vivo stratified ectocervical and columnar endocervical epithelium. Stratified and columnar cervical epithelia arise from two discrete unipotent stem cell populations of the endocervix. Unique stem cell signatures reveal a dependency on intrinsic Notch and Wnt microenvironmental signals. The genetic signatures of KRT5+ stratified vs KRT7+ columnar cervical cells establish discrete groups of cervical cancer of the squamous and adenocarcinoma types, respectively. Cervical tissue morphology is guided by the interplay of two discrete unipotent cervical stem cell populations and the spatio-temporal distribution of signals from the stroma.