Project description:Genomic analysis of many cancers has led to the identification of novel targets and the development of personalized, targeted therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. Clinical specimens typically contain variable degrees of non-tumor cells that can mask a potentially critical genomic signature, leaving important clinically relevant events undetected. When analysis is limited to a smaller number of specimens, the effects of heterogeneity within each sample is magnified. In light of these challenges, we used DNA content based flow cytometry to isolate clonal tumor populations from a series of rare cancers for genomic analysis: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. These purified clonal populations are then subject to high definition measurement of copy number aberrations by objectively measuring the height and boundaries of amplicons and by discriminating homozygous from partial deletions. Ranking of these events by copy number facilitates the identification of highly selected aberrations. This approach can garner useful information from a single biopsy. In the cases we describe, several potential therapeutic targets were identified and genomic aberrations correlated with the phenotypic behavior. We propose that clonal genomic analysis can generate unique hypotheses and guide the development of clinical advances for these and other rare tumors. We applied DNA content based flow sorting to isolate the nuclei of clonal populations from tumor biopsies. We coupled this strategy with oligonucleotide array CGH (aCGH) thereby obtaining high definition genomic profiles of clonal populations from different rare tumors including pancreatic neuroendocrine cancers, adrenal leiomyosarcoma, anal carcinoma, and cholangiocarcinoma.

Project description:The microarray gene expression pattern was studied using 798 different cancer cell lines. The cancer cell lines are obtained from different centers. Annotation information were provided in the supplementary file. golub-00327 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HT_HG-U133A Organism: Homo sapiens (ncbitax) Tissue Sites: leukemia, Urinary tract, Lung, BiliaryTract, Autonomic Ganglion, Thyroid gland, Stomach, Breast, Pancreas, Head and Neck, Lymphoma, Colorectal, Placenta, Liver, Brain, Bone, pleura, Skin, endometrium, Ovary, cervix, Oesophagus, Connective and Soft Tissue, Muscle, Kidney, Prostate, Adrenal Gland, Eye, Testis, Smooth Muscle Tissue, Vulva, Unknow Material Types: cell, synthetic_RNA, whole_organism, total_RNA, BVG Disease States: M3 acute myeloid leukemia, hairy cell leukemia, transitional cell carcinoma, Adenocarcinoma, B cell lymphoma unspecified, Acute Lymphoblastic Leukemia, blast phase chronic myeloid leukemia, Carcinoma, M6 acute myeloid leukemia, Neuroblastoma, follicular carcinoma, ductal carcinoma, Burkitt Lymphoma, Squamous Cell Carcinoma, M5 acute myeloid leukemia, Mycosis Fungoides and Sezary Syndrome, Acute T-Cell Lymphoblastic Leukemia, Adult T-Cell Leukemia/Lymphoma, M2 Therapy-Related Myeloid Neoplasm, Choriocarcinoma, Plasma Cell Myeloma, Hepatocellular Carcinoma, anaplastic large cell lymphoma, primitive neuroectodermal tumor-medulloblastoma, M4 acute myeloid leukemia, B Acute Lymphoblastic Leukemia, Acute Leukemia of Ambiguous Lineage, Osteosarcoma, Hodgkin Lymphoma, Mesothelioma, chondrosarcoma, Glioblastoma Multiforme, Malignant Melanoma, carcinosarcoma-malignant mesodermal mixed tumor, bronchioloalveolar adenocarcinoma, chronic lymphocytic leukemia-small lymphocytic lymphoma, micropapillary carcinoma, diffuse large B cell lymphoma, myelodysplastic syndrome, giant cell carcinoma, teratoma, multipotential sarcoma, Small Cell Carcinoma, ASTROCYTOMA, Fibrosarcoma, mucoepidermoid carcinoma, Rhabdomyosarcoma, L1 Acute T-Cell Lymphoblastic Leukemia, Glioma, Anaplastic Astrocytoma, Non-small cell carcinoma, Large Cell Carcinoma, mucinous carcinoma, Acute Myeloid Leukemia, malignant fibrous histiocytoma-pleomorphic sarcoma, clear cell carcinoma, B cell lymphoma unspecified, Anaplastic Carcinoma, Ewings sarcoma-peripheral primitive neuroectodermal tumor, undifferentiated carcinoma, Sarcoma, Embryonal Rhabdomyosarcoma, epithelioid sarcoma, renal cell carcinoma, carcinoid-endocrine tumor, Synovial Sarcoma, lymphoid neoplasm, rhabdoid tumor, Refractory Anemia with Excess Blasts, Liposarcoma, biphasic mesothelioma, adrenal cortical carcinoma, adenosquamous carcinoma, L2 Acute T-Cell Lymphoblastic Leukemia, chronic myeloid leukemia, Micropapillary Serous Carcinoma, desmoplastic, acute leukemia, Retinoblastoma, teratocarcinoma, clear cell renal cell carcinoma, Follicular Lymphoma, Wilms Tumor, M7 acute myeloid leukemia, gliosarcoma, embryonal carcinoma, Leiomyosarcoma, medullary carcinoma, granulosa cell tumor, papillary carcinoma, NS Acute Lymphoblastic Leukemia, papillary transitional cell carcinoma, small cell adenocarcinoma, epithelial dysplasia, hyperplasia, tubular adenocarcinoma, metaplasia, papillary ductal carcinoma, chronic eosinophilic leukemia-hypereosinophilic syndrome, #N/A, malignant trichilemmal cyst, Medullary Breast Carcinoma, L2 Acute Lymphoblastic Leukemia, Osteoblastic Osteosarcoma

Project description:This phase II trial studies nivolumab and ipilimumab in treating patients with rare tumors. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial enrolls participants for the following cohorts based on condition: 1. Epithelial tumors of nasal cavity, sinuses, nasopharynx: A) Squamous cell carcinoma with variants of nasal cavity, sinuses, and nasopharynx and trachea (excluding laryngeal, nasopharyngeal cancer [NPC], and squamous cell carcinoma of the head and neck [SCCHN]) B) Adenocarcinoma and variants of nasal cavity, sinuses, and nasopharynx (closed to accrual 07/27/2018) 2. Epithelial tumors of major salivary glands (closed to accrual 03/20/2018) 3. Salivary gland type tumors of head and neck, lip, esophagus, stomach, trachea and lung, breast and other location (closed to accrual) 4. Undifferentiated carcinoma of gastrointestinal (GI) tract 5. Adenocarcinoma with variants of small intestine (closed to accrual 05/10/2018) 6. Squamous cell carcinoma with variants of GI tract (stomach small intestine, colon, rectum, pancreas) (closed to accrual 10/17/2018) 7. Fibromixoma and low grade mucinous adenocarcinoma (pseudomixoma peritonei) of the appendix and ovary (closed to accrual 03/20/2018) 8. Rare pancreatic tumors including acinar cell carcinoma, mucinous cystadenocarcinoma or serous cystadenocarcinoma. Pancreatic adenocarcinoma is not eligible (closed to accrual) 9. Intrahepatic cholangiocarcinoma (closed to accrual 03/20/2018) 10. Extrahepatic cholangiocarcinoma and bile duct tumors (closed to accrual 03/20/2018) 11. Sarcomatoid carcinoma of lung 12. Bronchoalveolar carcinoma lung. This condition is now also referred to as adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma, or invasive mucinous adenocarcinoma 13. Non-epithelial tumors of the ovary: A) Germ cell tumor of ovary B) Mullerian mixed tumor and adenosarcoma (closed to accrual 03/30/2018) 14. Trophoblastic tumor: A) Choriocarcinoma (closed to accrual) 15. Transitional cell carcinoma other than that of the renal, pelvis, ureter, or bladder (closed to accrual) 16. Cell tumor of the testes and extragonadal germ tumors: A) Seminoma and testicular sex cord cancer B) Non seminomatous tumor C) Teratoma with malignant transformation (closed to accrual) 17. Epithelial tumors of penis - squamous adenocarcinoma cell carcinoma with variants of penis (closed to accrual) 18. Squamous cell carcinoma variants of the genitourinary (GU) system 19. Spindle cell carcinoma of kidney, pelvis, ureter 20. Adenocarcinoma with variants of GU system (excluding prostate cancer) (closed to accrual 07/27/2018) 21. Odontogenic malignant tumors 22. Pancreatic neuroendocrine tumor (PNET) (formerly named: Endocrine carcinoma of pancreas and digestive tract.) (closed to accrual) 23. Neuroendocrine carcinoma including carcinoid of the lung (closed to accrual 12/19/2017) 24. Pheochromocytoma, malignant (closed to accrual) 25. Paraganglioma (closed to accrual 11/29/2018) 26. Carcinomas of pituitary gland, thyroid gland parathyroid gland and adrenal cortex (closed to accrual) 27. Desmoid tumors 28. Peripheral nerve sheath tumors and NF1-related tumors (closed to accrual 09/19/2018) 29. Malignant giant cell tumors 30. Chordoma (closed to accrual 11/29/2018) 31. Adrenal cortical tumors (closed to accrual 06/27/2018) 32. Tumor of unknown primary (Cancer of Unknown Primary; CuP) (closed to accrual 12/22/2017) 33. Not Otherwise Categorized (NOC) Rare Tumors [To obtain permission to enroll in the NOC cohort, contact: S1609SC@swog.org] (closed to accrual 03/15/2019) 34. Adenoid cystic carcinoma (closed to accrual 02/06/2018) 35. Vulvar cancer (closed to accrual) 36. MetaPLASTIC carcinoma (of the breast) (closed to accrual) 37. Gastrointestinal stromal tumor (GIST) (closed to accrual 09/26/2018) 38. Perivascular epithelioid cell tumor (PEComa) 39. Apocrine tumors/extramammary Paget’s disease (closed to accrual) 40. Peritoneal mesothelioma 41. Basal cell carcinoma (temporarily closed to accrual 04/29/2020) 42. Clear cell cervical cancer 43. Esthenioneuroblastoma (closed to accrual) 44. Endometrial carcinosarcoma (malignant mixed Mullerian tumors) (closed to accrual) 45. Clear cell endometrial cancer 46. Clear cell ovarian cancer (closed to accrual) 47. Gestational trophoblastic disease (GTD) 48. Gallbladder cancer 49. Small cell carcinoma of the ovary, hypercalcemic type 50. PD-L1 amplified tumors 51. Angiosarcoma 52. High-grade neuroendocrine carcinoma (pancreatic neuroendocrine tumor [PNET] should be enrolled in Cohort 22; prostatic neuroendocrine carcinomas should be enrolled into Cohort 53). Small cell lung cancer is not eligible (closed to accrual) 53. Treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC)

Project description:Two prognostically significant subtypes of high-grade lung neuroendocrine tumors independent of small-cell and large-cell neuroendocrine carcinomas identified by gene expression profiles. BACKGROUND: Classification of high-grade neuroendocrine tumors (HGNT) of the lung currently recognises large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung carcinoma (SCLC) as distinct groups. However, a similarity in histology for these two carcinomas and uncertain clinical course have led to suggestions that a single HGNT classification would be more appropriate. Gene expression profiling, which can reproduce histopathological classification, and often defines new subclasses with prognostic significance, can be used to resolve HGNT classification. METHODS: We used cDNA microarrays with 40386 elements to analyze the gene expression profiles of 38 surgically resected samples of lung neuroendocrine tumors and 11 SCLC cell lines. Samples of large-cell carcinoma, adenocarcinoma, and normal lung were also included to give a total of 105 samples analyzed. The data were subjected to filtering to yield informative genes before unsupervised hierarchical clustering that identified relatedness of tumor samples. FINDINGS: Distinct groups for carcinoids, large-cell carcinoma, adenocarcinoma, and normal lung were readily identified. However, we were unable to distinguish LCNEC from SCLC by gene expression profiling. Three independent rounds of unsupervised hierarchical clustering consistently divided SCLC samples into two main groups with LCNEC samples largely integrated with these groups. Furthermore, patients in one of the groups identified by clustering had a significantly better clinical outcome than the other (83% vs 12% survived for 5 years; p=0.0094. None of the highly proliferative SCLC cell lines subsequently analyzed clustered with this good-prognosis group. INTERPRETATION: Our findings show that HGNT of the lung can be classified into two groups independent of SCLC and LCNEC. To this end, we have identified many genes, some of which encode well-characterized markers of cancer that distinguish the HGNT groups. These results have implications for the diagnosis, classification, and treatment of lung neuroendocrine tumors, and provide important insights into their underlying biology. Keywords: other

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345624ec-73e4-4be4-b55c-ec45d08b0138 - samples

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