The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Multiregion whole-exome sequencing of intraductal papillary mucinous neoplasms reveals frequent somatic KLF4 mutations predominantly in low-grade regions
Open accessAbstract
Objective: Intraductal papillary mucinous neoplasms (IPMNs) are non-invasive precursor lesions that can progress to invasive pancreatic cancer and are classified as low-grade or high-grade based on the morphology of the neoplastic epithelium. We aimed to compare genetic alterations in low-grade and high-grade regions of the same IPMN in order to identify molecular alterations underlying neoplastic progression. Design: We performed multiregion whole exome sequencing on tissue samples from 17 IPMNs with both low-grade and high-grade dysplasia (76 IPMN regions, including 49 from low-grade dysplasia and 27 from high-grade dysplasia). We reconstructed the phylogeny for each case, and we assessed mutations in a novel driver gene in an independent cohort of 63 IPMN cyst fluid samples. Results: Our multiregion whole exome sequencing identified KLF4, a previously unreported genetic driver of IPMN tumorigenesis, with hotspot mutations in one of two codons identified in >50% of the analyzed IPMNs. Mutations in KLF4 were significantly more prevalent in low-grade regions in our sequenced cases. Phylogenetic analyses of whole exome sequencing data demonstrated diverse patterns of IPMN initiation and progression. Hotspot mutations in KLF4 were also identified in an independent cohort of IPMN cyst fluid samples, again with a significantly higher prevalence in low-grade IPMNs. Conclusion: Hotspot mutations in KLF4 occur at high prevalence in IPMNs. Unique among pancreatic driver genes, KLF4 mutations are enriched in low-grade IPMNs. These data highlight distinct molecular features of low-grade and high-grade dysplasia and suggest diverse pathways to high-grade dysplasia via the IPMN pathway.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“KRAS mutations are observed in most low-grade PanINs and IPMNs, suggesting KRAS is the initiating genetic event driving exocrine neoplasia46,47.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [47]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
Mutational heterogeneity in cancer and the search for new cancer-associated genes
Lawrence, M. S., Stojanov, P., Polak, P., Kryukov, G. V., Cibulskis, K., Sivachenko, A., Carter, S. L., Stewart, C., Mermel, C. H., Roberts, S. A., et al. (2013) · Nature · doi:10.1038/nature12213 · Cited by 5,461
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, K., Lawrence, M. S., Carter, S. L., Sivachenko, A., Jaffe, D. B., Sougnez, C. L., Gabriel, S., Meyerson, M. M., Lander, E. S., & Getz, G. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2514 · Cited by 4,965
Genomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621
Self-citationDetection and localization of surgically resectable cancers with a multi-analyte blood test
Cohen, J. D., Li, L., Wang, Y., Thoburn, C., Afsari, B., Danilova, L., Douville, C., Javed, A. A., Wong, F., Mattox, A., et al. (2018) · Science · doi:10.1126/science.aar3247 · Cited by 2,783
Self-citationIntegrated genomic characterization of pancreatic ductal adenocarcinoma
Raphael, B. J., Hruban, R. H., Aguirre, A. J., Moffitt, R. A., Yeh, J. J., Stewart, C., Robertson, A. G., Cherniack, A. D., Gupta, M., Getz, G., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.007 · Cited by 2,019
Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas
Tanaka, M., Fernández-del Castillo, C., Kamisawa, T., Jang, J. Y., Levy, P., Ohtsuka, T., Salvia, R., Shimizu, Y., Tada, M., & Wolfgang, C. L. (2017) · Pancreatology · doi:10.1016/j.pan.2017.07.007 · Cited by 1,797
Self-citationDetection and quantification of rare mutations with massively parallel sequencing
Kinde, I., Wu, J., Papadopoulos, N., Kinzler, K. W., & Vogelstein, B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105422108 · Cited by 1,144
Vege, S. S., Ziring, B., Jain, R., Moayyedi, P., Adams, M. A., Dorn, S. D., Dudley-Brown, S. L., Flamm, S. L., Gellad, Z. F., Gruss, C. B., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.01.015 · Cited by 1,138
Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets
Witkiewicz, A. K., McMillan, E. A., Balaji, U., Baek, G., Lin, W.-C., Mansour, J., Mollaee, M., Wagner, K.-U., Koduru, P., Yopp, A., et al. (2015) · Nature Communications · doi:10.1038/ncomms7744 · Cited by 1,115
Flagged first, then by citations
Cited by
Sorted by citations
Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321
Early detection of pancreatic cancer using DNA-based molecular approaches
Singhi, A. D., & Wood, L. D. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00470-0 · Cited by 127
Self-citation
Metadata
- Authors
- Fujikura, K., Hosoda, W., Felsenstein, M., Song, Q., Reiter, J. G., Zheng, L., Beleva Guthrie, V., Rincon, N., Dal Molin, M., Dudley, J., Cohen, J. D., Wang, P., Fischer, C. G., Braxton, A. M., Noë, M., Jongepier, M., Fernández-del Castillo, C., Mino-Kenudson, M., Schmidt, C. M., Yip-Schneider, M. T., Lawlor, R. T., Salvia, R., Roberts, N. J., Thompson, E. D., Karchin, R., Lennon, A. M., Jiao, Y., & Wood, L. D.
- Affiliations
- Johns Hopkins University (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Stanford Medicine (US)
- Personal Genome Diagnostics, Baltimore, Maryland, USA
- Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Harvard University (US)
- Indiana University School of Medicine (US)
- University of Verona (IT)
- Corresponding author
- Wood, Laura D
- ORCID
- Fujikura, Kohei
- Hosoda, Waki
- Felsenstein, Matthäus
- Reiter, Johannes G
- Zheng, Lily
- Rincon, Natalia
- Dudley, Jonathan
- Cohen, Joshua D
- Braxton, Alicia M
- Noë, Michaël
- Mino-Kenudson, Mari
- Schmidt, C Max
- Yip-Schneider, Michele T
- Lawlor, Rita T
- Salvia, Roberto
- Roberts, Nicholas J
- Thompson, Elizabeth D
- Karchin, Rachel
- Lennon, Anne Marie
- Jiao, Yuchen
- Wood, Laura D
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2020-10-07
- Volume
- 70
- Issue
- 5
- Pages
- 928-939
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC8262510
- OpenAlex
- W3092302697
- Cited by
- 89
- References
- 49
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 17 · 2023: 19 · 2022: 13 · 2021: 11
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Funders
- American Cancer Society (RSG-18-143-01-CSM)
- Kaya Tuncer Career Development Award in Gastrointestinal Cancer Prevention
- Rolfe Pancreatic Cancer Foundation
- Joseph C Monastra Foundation
- CAMS Innovation Fund for Medical Sciences (2016-I2M-1-001, 2019-I2M-1-001)
- The Gerald O Mann Charitable Foundation
- American Gastroenterological Association (AGA-Bernard Lee Schwartz Foundation Research Schol)
- Carol S. and Robert M. Long Pancreatic Cancer Research Fund
- Susan Wojcicki and Denis Troper
- Sidney Kimmel Foundation for Cancer Research (Kimmel Scholar Award)
- Emerson Collective Cancer Research Fund
- Associazione Italiana Ricerca Cancro (12182)
- Buffone Family Gastrointestinal Cancer Research Fund
- Virginia and D.K. Ludwig Fund for Cancer Research
- Sol Goldman Sequencing Facility at Johns Hopkins
- National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK107781)
- Sol Goldman Pancreatic Cancer Research Center
- Howard Hughes Medical Institute
- American Association for Cancer Research (AACR-Incyte Corporation Career Development Award f)
- Lustgarten Foundation
- National Cancer Institute (P50 CA62924)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- intraductal papillary mucinous neoplasm, low-grade dysplasia, high-grade dysplasia, pancreatic cancer progression, somatic mutations, tumor phylogeny, cyst fluid
- MeSH terms
- Exome Sequencing, Pancreatic Intraductal Neoplasms, Kruppel-Like Factor 4, Adenocarcinoma, Mucinous, Carcinoma, Papillary, Humans, Mutation, Retrospective Studies, Biomarkers, Tumor, Neoplasm Grading
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
