Nandita Barnabas

We reviewed the phenotypic and molecular characteristics of MCF10DCIS.com and the SUM cell lines based on numerous studies performed over the years. The major signaling pathways that give rise to the phenotype of these cells may serve as a good resource of information when researchers in drug discovery and development use these cells to identify novel targets and biomarkers. Major signaling pathways and mutations affecting the coding sequence are also described providing important information when using these cells as a model in a variety of studies.

BACKGROUND: Radical prostatectomy (RP) is not curative if patients have undetected metastatic prostate cancer. Markers that indicate the presence of metastatic disease would identify men who may benefit from systemic adjuvant therapy. Our approach was to analyze the primary tumors of men with metastatic disease versus organ-confined disease to identify molecular changes that distinguish between these groups. METHODS: Patients were identified based on long-term follow-up of serum prostate specific antigen (PSA) levels following RP. We compared the tumors of African American (AA) men with undetectable serum PSA for >9 year after RP (good outcome) versus those of AA men with a rising PSA and recurrence after radiation or androgen ablation or both (poor outcome). We used real-time quantitative PCR to assay gene copy number alterations in tumor DNA relative to patient-matched non-tumor DNA isolated from paraffin-embedded tissue. We assayed several genes located in the specific regions of chromosome 8p and 8q that frequently undergo loss and/or gain, respectively, in prostate cancer, and the androgen receptor gene at Xq12. RESULTS: Gain of the MIR151 gene at 8q24.3 (in 33% of poor outcome vs. 6% of good outcome tumors) and/or loss of the NKX3-1 gene at 8p21.2 (in 39% of poor outcome vs. 11% of good outcome tumors) affected 67% of poor outcome tumors, compared to only 17% of good outcome tumors. CONCLUSIONS: Copy number gain of the MIR151 gene and/or loss of the NKX3-1 gene in the primary tumor may indicate the presence of metastatic disease.

BACKGROUND AND OBJECTIVES: Renal cell carcinomas (RCC) with abundant granular cytoplasm include oncocytomas, eosinophilic variants of chromophobe RCC, papillary RCC, collecting duct carcinoma, and some conventional (clear cell) RCC. Tumors with predominantly clear cell cytoplasm include typical chromophobe RCC and conventional (clear cell) RCC. The objective of this study was to determine if mutations in the VHL gene can serve as auxiliary diagnostic criteria in refining histology based subtyping of renal epithelial neoplasia. METHODS: The study cohort of 67 cases included 24 conventional RCC, 14 chromophobe RCC, 14 papillary RCC, and 15 oncocytomas. Single strand conformational polymorphism (SSCP) was used as a screening procedure for mutations followed by automated sequencing to identify mutations. RESULTS: Thirteen of the 14 mutations identified were novel, seven of which were in the coding region. In chromophobe RCC, mutations clustered in the 5'UTR/promoter region and have not been previously reported. Exon 3 appeared to favor conventional (clear cell) RCC and correlated with a more aggressive phenotype. Mutations were absent in the papillary and oncocytoma RCC subtypes. CONCLUSIONS: Exon 3 mutations permitted a morphological distinction between conventional (clear cell) RCC and chromophobe RCC with clear cells. Mutations in the VHL gene refine histologic diagnostic criteria in RCC serving as adjuncts to the present morphology based diagnosis of RCC.

BACKGROUND: In patients with B-cell chronic lymphocytic leukemia (CLL), considerable disease heterogeneity within clinical stages necessitates the search for relevant prognostic indicators, particularly those that may help to determine the need for early therapeutic intervention. In the current study, the authors investigated the role of p53 mutations and chromosomal abnormalities in 30 patients with CLL. METHODS: Thirty patients were screened for p53 mutations. Half of the group had aggressive disease characterized by leucocytosis, lymph node enlargement, organomegaly, and shortened tumor doubling time. Because 95% of p53 mutations reside in "hot-spot" regions of exons 5-9 of the p53 gene, the authors sequenced these exons completely for mutation detection. RESULTS: Sequence analysis identified p53 mutations in 14 of 30 patients that were distributed equally among patients with aggressive disease and nonaggressive disease. There were six mutations in exon 7, five mutations in exon 5, and one mutation each in exons 6 and 8. Five of 15 patients with clinically aggressive disease had mutations in exon 7. Only one patient with nonaggressive disease had an exon 7 mutation. Abnormal cytogenetics were present in 22 of 30 patients (73%). Most patients with the p53 mutation (13 of 14 patients; 93%) displayed abnormal cytogenetics. Twelve of 15 patients with aggressive disease and 9 of 15 patients with average disease exhibited abnormal karyotypes. CONCLUSIONS: The presence of p53 mutations did not predict clinical behavior or disease outcome, although the frequency of mutations appears to be higher than reported previously. In this study, mutations of exon 7 (5 of 6 patients) occurred in patients with clinically aggressive disease. The significance of this observation warrants further examination.