Project description:Proliferative breast lesions, such as simple ductal hyperplasia (SH) and atypical ductal hyperplasia (ADH), are candidate precursors to ductal carcinoma in situ (DCIS) and invasive cancer. To better understand their relationship to more advanced disease, we used microdissection and DNA microarrays to profile the gene expression of patient-matched histologically normal (HN), ADH, and DCIS from 12 patients with ER+ sporadic breast cancer. SH were profiled from a subset of cases. We found 837 differentially expressed genes between DCIS-HN and 447 between ADH-HN, with >90% of the ADH-HN genes also present among the DCIS-HN genes. Only 61 genes were identified between ADH-DCIS. Expression differences were reproduced in an independent cohort of patient-matched lesions by qRT-PCR. Many breast cancer-related genes and pathways were dysregulated in ADH and maintained in DCIS. Particularly, cell adhesion and extracellular matrix (ECM) interactions were overrepresented. Focal adhesion was the top pathway in each gene set. We conclude that ADH and DCIS share highly similar gene expression and are distinct from HN. In contrast, SH appear more similar to HN. These data provide genetic evidence that ADH (but not SH) are often precursors to cancer and suggest cancer-related genetic changes, particularly adhesion and ECM pathways, are dysregulated prior to invasion and even before malignancy is apparent. These findings could lead to novel risk stratification, prevention, and treatment approaches. Patient-matched (HN, SH, ADH, DCIS) samples were isolated from within patients with ER+ sporadic breast cancers via laser capture microdissection. Use of patient-matched samples decreases between patient variations.
Project description:Here, we investigated tumor tissue from 26 patients affected by AT/RT to identify signatures of recurrences in comparison to matched primary tumor samples.
Project description:We report sequencing of 10 SCC_NodalMet samples from human subjects. Sequencing was done on an oncology targeted gene mutation panel consisting of 76 genes.
Project description:Prostate adenocarcinoma and matched adjacent normal samples were profiled by deep transcriptional sequencing to analyze transcription-induced chimeras and gene fusions. Reference samples from the MAQC and brain and universal reference libraries were also sequenced.
Project description:As part of a clinical trial of the MDM2 inhibitor DS-3032b, 41 primary tumor samples were obtained before treatment from 38 patients newly diagnosed with AML, or relapsed or refractory to standard induction chemotherapy Gene expression features of pretreatment samples, along with TP53 mutation status, were found to correlate with clinical response to DS-3032b (manuscript under review).
Project description:Here, we investigated tumor tissue from 26 patients affected by AT/RT to identify signatures of recurrences in comparison to matched primary tumor samples. Therefore, we performed histological analysis and DNA methylation and gene expression profiling.
Project description:Despite aggressive multi-modal treatment, advanced head and neck squamous cell carcinoma (HNSCC) patients are at high risk of recurrence. Matched pairs (n=38) of primary/recurrent tumors were subjected to whole exome and RNA sequencing. Mutational landscapes and genomic copy number alterations indicated diverging clonal origins in a subset of cases. Transcriptional subtyping (classical/CL, basal/BA, inflamed-mesenchymal/IMS) in primary and recurrent HNSCC (n=112) revealed more frequent CL and IMS in primary tumors with low recurrence rates and a prevalence of BA in recurrent tumors associated with p-EMT and early recurrence. 44% of matched cases underwent a subtype change from primary to recurrent tumors, preferably from IMS to BA or CL. In recurrences, HYPOXIA, P-EMT and RADIATION RESISTANCE signatures were up- and TUMOR INFLAMMATION down-regulated compared to index tumors. A therapy-induced selection of transcriptional subtypes demonstrates the importance of molecular characterization of recurrences for second-line therapy decisions to enable optimally tailored treatments.
Project description:Despite aggressive multi-modal treatment, advanced head and neck squamous cell carcinoma (HNSCC) patients are at high risk of recurrence. Matched pairs (n=38) of primary/recurrent tumors were subjected to whole exome and RNA sequencing. Mutational landscapes and genomic copy number alterations indicated diverging clonal origins in a subset of cases. Transcriptional subtyping (classical/CL, basal/BA, inflamed-mesenchymal/IMS) in primary and recurrent HNSCC (n=112) revealed more frequent CL and IMS in primary tumors with low recurrence rates and a prevalence of BA in recurrent tumors associated with p-EMT and early recurrence. 44% of matched cases underwent a subtype change from primary to recurrent tumors, preferably from IMS to BA or CL. In recurrences, HYPOXIA, P-EMT and RADIATION RESISTANCE signatures were up- and TUMOR INFLAMMATION down-regulated compared to index tumors. A therapy-induced selection of transcriptional subtypes demonstrates the importance of molecular characterization of recurrences for second-line therapy decisions to enable optimally tailored treatments.