ArticleCancer research2014
CLPTM1L promotes growth and enhances aneuploidy in pancreatic cancer cells.
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In one paragraph
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 4 of them syntheses that pooled it.
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0cells of the map it votes in
47citing papers in PubMed, 4 pooled it
3.5field-weighted citation impact, top 7% of its field
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The trial behind it
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Who cites it
47 citing papers in PubMed, 4 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Pooled it
- Cumulative Evidence for Relationships Between Multiple Variants in the TERT and CLPTM1L Region and Risk of Cancer and Non-Cancer Disease.Frontiers in oncology · 2022Pooled it
- Telomere structure and maintenance gene variants and risk of five cancer types.International journal of cancer · 2016Pooled it
- Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.Nature genetics · 2014Pooled it
- Candidate locus analysis of the TERT-CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk.Human genetics · 2015Trial
- Characterization of a pancreatic cancer GWAS signal suggests PDX1 buffers stress in the exocrine pancreas.medRxiv : the preprint server for health sciences · 2026Article
- Integrative screening identifies functional variants and VNTRs underlying GWAS signals at the 5p15.33 multi-cancer susceptibility locus.medRxiv : the preprint server for health sciences · 2026Article
- TWAS atlas 2.0: an updated data resource for transcriptome-wide association studies.Nucleic acids research · 2026Article
- A genome-wide association study integrated with single-cell and bulk profiles uncovers susceptibility genes for nasopharyngeal carcinoma involved in tumorigenesis via regulation of T cells.Genome biology · 2025Article
- Investigating the Shared Genetic Architecture Between Leukocyte Telomere Length and Prostate Cancer.The world journal of men's health · 2025Article
- Genetic regulation of TERT splicing affects cancer risk by altering cellular longevity and replicative potential.Nature communications · 2025Article
- Cleft lip and palate transmembrane protein 1-like is a putative regulator of tumorigenesis and sensitization of cervical cancer cells to cisplatin.Frontiers in oncology · 2024Article
- Structure and Function of the Glycosylphosphatidylinositol Transamidase, a Transmembrane Complex Catalyzing GPI Anchoring of Proteins.Sub-cellular biochemistry · 2024Review
- Exploring the Relationship betweenGenes · 2023Article
- CLPTM1L expression predicts recurrence of patients with intermediate‑ and high‑risk stage IB‑IIB cervical cancer undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.Oncology letters · 2023Article
- Role of microRNA-494 in tumor progression.American journal of translational research · 2023Review
- Functional characterization of 5p15.33 risk locus in uveal melanoma reveals rs452384 as a functional variant and NKX2.4 as an allele-specific interactor.American journal of human genetics · 2022Article
- Genome-wide CRISPR screen reveals CLPTM1L as a lipid scramblase required for efficient glycosylphosphatidylinositol biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Different Pigmentation Risk Loci for High-Risk Monosomy 3 and Low-Risk Disomy 3 Uveal Melanomas.Journal of the National Cancer Institute · 2022Article
- TERT genetic polymorphismFrontiers in surgery · 2022Article
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 1 country.
Jinping JiaAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Allen D BosleyAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Abbey ThompsonAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Jason W HoskinsAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Adam CheukAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Irene CollinsAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Hemang ParikhAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Zhen XiaoAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Kris YlayaAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Marta DzyadykAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Wendy CozenAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Brenda Y HernandezAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Charles F LynchAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Jadranka LoncarekAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Sean F AltekruseAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Lizhi ZhangAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Christopher J WestlakeAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Valentina M FactorAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Snorri ThorgeirssonAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
William R BamletAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Stephen M HewittAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Gloria M PetersenAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Thorkell AndressonAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Laufey T AmundadottirAuthors' Affiliations: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics; Pediatric Oncology Branch; Laboratory of Pathology; Division of Cancer Control and Population Sciences; Laboratory of Experimental Carcinogenesis, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda; Laboratory of Proteomics and Analytical Technologies, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research; Laboratory of Protein Dynamics and Signaling and Laboratory of Cell & Developmental Signaling, NCI-Frederick, Frederick, Maryland; Keck School of Medicine, University of Southern California, Los Angeles, California; University of Hawaii Cancer Center, Honolulu, Hawaii; Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, Iowa; and Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota amundadottirl@mail.nih.gov.
University of Hawaii System · USUniversity of Hawaiʻi at Mānoa · USLeidos (United States) · USNational Cancer Institute · USMayo Clinic in Florida · USFrederick National Laboratory for Cancer Research · US
Funding
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3MLaboratory of Translational GenomicsZIACP010201 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI PROKUNINA-OLSSON, LIUDMILA · 2010 to 2025
$91.2MUniversity of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI Xin Chen · 1996 to 2026
$56.2MTissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI PETERSEN, GLORIA M. · 2004 to 2018
$32.7MINSTITUTIONAL TRAINING GRANT IN GENOME SCIENCET32HG000044 · NHGRI · STANFORD UNIVERSITY · PI MICHAEL P. SNYDER · 1995 to 2026
$32.2MWhole Genome Scan in the Pancreatic Cancer Cohort Consortium (PanScan)ZIACP010193 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI STOLZENBERG-SOLOMON, RACHAEL · 2009 to 2025
$9.5MApplied Molecular Pathology LaboratoryZICBC011257 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HEWITT, STEPHEN · 2010 to 2014
$1.2MIntramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA CP010193NCI NIH HHS P30 CA015083NCI NIH HHS P50 CA102701NHGRI NIH HHS T32 HG000044
Abstract
Genome-wide association studies (GWAS) of 10 different cancers have identified pleiotropic cancer predisposition loci across a region of chromosome 5p15.33 that includes the TERT and CLPTM1L genes. Of these, susceptibility alleles for pancreatic cancer have mapped to the CLPTM1L gene, thus prompting an investigation of the function of CLPTM1L in the pancreas. Immunofluorescence analysis indicated that CLPTM1L localized to the endoplasmic reticulum where it is likely embedded in the membrane, in accord with multiple predicted transmembrane domains. Overexpression of CLPTM1L enhanced growth of pancreatic cancer cells in vitro (1.3-1.5-fold; PDAY7 < 0.003) and in vivo (3.46-fold; PDAY68 = 0.039), suggesting a role in tumor growth; this effect was abrogated by deletion of two hydrophilic domains. Affinity purification followed by mass spectrometry identified an interaction between CLPTM1L and non-muscle myosin II (NMM-II), a protein involved in maintaining cell shape, migration, and cytokinesis. The two proteins colocalized in the cytoplasm and, after treatment with a DNA-damaging agent, at the centrosomes. Overexpression of CLPTM1L and depletion of NMM-II induced aneuploidy, indicating that CLPTM1L may interfere with normal NMM-II function in regulating cytokinesis. Immunohistochemical analysis revealed enhanced staining of CLPTM1L in human pancreatic ductal adenocarcinoma (n = 378) as compared with normal pancreatic tissue samples (n = 17; P = 1.7 × 10(-4)). Our results suggest that CLPTM1L functions as a growth-promoting gene in the pancreas and that overexpression may lead to an abrogation of normal cytokinesis, indicating that it should be considered as a plausible candidate gene that could explain the effect of pancreatic cancer susceptibility alleles on chr5p15.33.
Indexed as
AneuploidyAnimalsCarcinoma, Pancreatic DuctalCell Growth ProcessesCell Line, TumorFemaleHEK293 CellsHeterograftsHumansMembrane ProteinsMiceMice, NudeMyosin Type IINeoplasm ProteinsPancreatic NeoplasmsSubcellular FractionsCLPTM1L protein, humanMembrane ProteinsMyosin Type IINeoplasm Proteins
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