Chromosome arm 3p has been widely recognized to harbor one or more tumor suppressor genes important in the development or progression of lung cancer. The minimally deleted region is quite extensive however, including over 60% of the short arm from 3p14 to p23 in SCLC. In non-SCLC, the minimally deleted region is smaller but less well defined; it appears to center around the 3p14 locus D3S3. Recent identification of an SCLC cell line with a submicroscopic deletion, the U2020 cell line, affords an opportunity to intensively investigate one small region of 3p for the presence of lung cancer associated tumor suppressor genes. the U2020 deletion is estimated to remove 4 to 5 megabases of 3p including the 3p14 locus D3S3. We have identified 7 additional markers deleted in U2020 and physically linked most of them over a region of 3.5 megabases. We have isolated yeast artificial chromosome (YAC) clones for all these markers and assembled many into contiguous cloned segments. the 33 YACs isolated so far contain about 4 megabases of the U2020 deletion. This proposal will use these YAC resources to develop a series of highly polymorphic markers along the U2020 deletion, and other selected regions of 3p. These polymorphic markers will then be used to survey lung tumors for loss of heterozygosity or small, homozygous or overlapping deletions. Tumors available for this analysis include up to 500 matched tumor-normal samples comprising non-SCLC cases and up to 200 unmatched SCLC cell lines. the primary aim of this proposal is to significantly narrow the target region within U2020 to uncover the location of one putative lung cancer tumor suppressor gene. this project will lay the foundation for future isolation and intensive study of this critically important tumor suppressor.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
1P50CA058187-01
Application #
3796262
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Type
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
McCoach, Caroline E; Le, Anh T; Gowan, Katherine et al. (2018) Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non-small Cell Lung Cancer. Clin Cancer Res 24:3334-3347
Drilon, Alexander; Laetsch, Theodore W; Kummar, Shivaani et al. (2018) Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378:731-739
Pilling, Amanda B; Kim, Jihye; Estrada-Bernal, Adriana et al. (2018) ALK is a critical regulator of the MYC-signaling axis in ALK positive lung cancer. Oncotarget 9:8823-8835
Kwak, Jeff W; Laskowski, Jennifer; Li, Howard Y et al. (2018) Complement Activation via a C3a Receptor Pathway Alters CD4+ T Lymphocytes and Mediates Lung Cancer Progression. Cancer Res 78:143-156
Sakamoto, Mandy R; Honce, Justin M; Lindquist, Deborah L et al. (2018) Lorlatinib Salvages CNS Relapse in an ALK-Positive Non-Small-Cell Lung Cancer Patient Previously Treated With Crizotinib and High-Dose Brigatinib. Clin Lung Cancer :
McCoach, Caroline E; Blakely, Collin M; Banks, Kimberly C et al. (2018) Clinical Utility of Cell-Free DNA for the Detection of ALK Fusions and Genomic Mechanisms of ALK Inhibitor Resistance in Non-Small Cell Lung Cancer. Clin Cancer Res 24:2758-2770
Geraci, Mark W (2018) TARGETING THE PROSTACYCLIN/PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA AXIS IN LUNG CANCER CHEMOPREVENTION. Trans Am Clin Climatol Assoc 129:48-55
Robichaux, Jacqulyne P; Elamin, Yasir Y; Tan, Zhi et al. (2018) Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med 24:638-646
Kimball, Abigail K; Oko, Lauren M; Bullock, Bonnie L et al. (2018) A Beginner's Guide to Analyzing and Visualizing Mass Cytometry Data. J Immunol 200:3-22
Tippimanchai, Darinee D; Nolan, Kyle; Poczobutt, Joanna et al. (2018) Adenoviral vectors transduce alveolar macrophages in lung cancer models. Oncoimmunology 7:e1438105

Showing the most recent 10 out of 435 publications