Project description:Oral cancer is an aggressive malignancy with a survival rate below 50% in advanced stages due to low mutation rates, lack of molecular subtypes, and limited treatment targets. This study presents a pioneering approach to classifying oral cancer subtypes based on the morphology of patient-derived organoids (PDOs) and proposes a novel therapeutic strategy. We successfully established 76 cancer and 81 normal PDOs. For cancer PDOs, both manual classification and AI-based scoring were utilized to categorize them into three distinct subtypes: normal-like, dense, and grape-like. These subtypes correlated with unique transcriptomic profiles, genetic mutations, and clinical outcomes, with patients harboring dense and grape-like organoids exhibiting poorer prognoses. Furthermore, drug response assessments of 14 single agents and Cisplatin combination therapies identified a synergistic treatment approach for resistant subtypes. This study highlights the potential of integrating morphology-based classification with genomic and transcriptomic analyses to refine oral cancer subtyping and develop effective treatment strategies.
Project description:Oral cancer is an aggressive malignancy with a survival rate below 50% in advanced stages due to low mutation rates, lack of molecular subtypes, and limited treatment targets. This study presents a pioneering approach to classifying oral cancer subtypes based on the morphology of patient-derived organoids (PDOs) and proposes a novel therapeutic strategy. We successfully established 76 cancer and 81 normal PDOs. For cancer PDOs, both manual classification and AI-based scoring were utilized to categorize them into three distinct subtypes: normal-like, dense, and grape-like. These subtypes correlated with unique transcriptomic profiles, genetic mutations, and clinical outcomes, with patients harboring dense and grape-like organoids exhibiting poorer prognoses. Furthermore, drug response assessments of 14 single agents and Cisplatin combination therapies identified a synergistic treatment approach for resistant subtypes. This study highlights the potential of integrating morphology-based classification with genomic and transcriptomic analyses to refine oral cancer subtyping and develop effective treatment strategies.
Project description:Infinium 450k data from three HCV-infection patients. Ten cirrhotic nodules were isolated from each patient for genome-wide DNA methylation analysis. One case had an incedental tumor that was also processed.
Project description:To define the sources and the extent of heterogeneity, we performed an in-depth analysis of the genomic architecture of three chemoradiation-naïve breast cancers with well-defined clinical features including variable ER, PR, Her2 receptor expression and distinct pathogenic BRCA2mut genotypes. The latter included a germ line carrier and a patient with a somatic variant. In each case we combined DNA content-based flow cytometry with whole exome sequencing and genome wide copy number variant (CNV) analysis of distinct populations sorted from multiple (4-18) mapped biopsies within the tumors and involved lymph nodes. Interrogating flow-sorted tumor populations from each biopsy provided an objective method to distinguish fixed and variable genomic lesions in each tumor. Notably we show that tumors exploit CNVs to enrich fixed mutations and deletions that are shared throughout each tumor. The identification of fixed genomic lesions in distinct populations, that are shared or unique within each tumor, has broad implications for the study of tumor heterogeneity including the presence of tumor markers and therapeutic targets, and of candidate neoepitopes in breast and other solid tumors that can advance more effective treatment and clinical management of patients with disease.
Project description:DNA copy number analysis of myxoinflammatory fibroblastic sarcomas, and related lesions, using 32k BAC array CGH. All four cases analyzed with array CGH showed amplification of the region 86.30-87.74 Mb in 3p11.1-12.1. No additional aberration was detected in more than two tumors, except for the deletion distal to the amplification on chromosome 3. Case 1 showed deletion affecting the region from the centromere of chromosome 1 to the 5'-end of TGFBR3. Homozygous deletion was found in one case (case 6) affecting the region 21.08-22.15 Mb on chromosome arm 9p harboring the CDKN2A and CDKN2B genes.