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KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: implications for the human pancreatic cancer cell of origin.

Publication ,  Journal Article
Shi, C; Hong, S-M; Lim, P; Kamiyama, H; Khan, M; Anders, RA; Goggins, M; Hruban, RH; Eshleman, JR
Published in: Mol Cancer Res
February 2009

Pancreatic intraepithelial neoplasia (PanIN) is a precursor to invasive ductal adenocarcinoma of the pancreas. Observations made in genetically engineered mouse models suggest that the acinar/centroacinar compartment can give rise to ductal neoplasia. To integrate findings in mice and men, we examined human acinar cells, acinar-ductal metaplasia (ADM) lesions, and PanINs for KRAS2 gene mutations. Surgically resected pancreata were screened for foci of ADM with or without an associated PanIN lesion. Stromal cells, acinar cells, ADMs, and PanINs were separately isolated using laser capture microdissection. KRAS2 status was analyzed using genomic DNA isolated from the microdissected tissue. Twelve of these 31 foci of ADM occurred in isolation, whereas 19 were in the same lobules as a PanIN lesion. All 31 microdissected foci of acinar cells were KRAS2 gene wild-type, as were all 12 isolated ADM lesions lacking an associated PanIN. KRAS2 gene mutations were present in 14 of 19 (74%) PanIN lesions and in 12 of the 19 (63%) foci of ADM associated with these PanINs. All ADM lesions with a KRAS2 gene mutation harbored the identical KRAS2 gene mutation found in their associated PanIN lesions. Ductal neoplasms of the human pancreas, as defined by KRAS2 gene mutations, do not appear to arise from acinar cells. Isolated AMD lesions are genetically distinct from those associated with PanINs, and the latter may represent retrograde extension of the neoplastic PanIN cells or less likely are precursors to PanIN.

Duke Scholars

Published In

Mol Cancer Res

DOI

ISSN

1541-7786

Publication Date

February 2009

Volume

7

Issue

2

Start / End Page

230 / 236

Location

United States

Related Subject Headings

  • ras Proteins
  • Stromal Cells
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogene Proteins
  • Polymerase Chain Reaction
  • Pancreatic Neoplasms
  • Pancreas
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shi, C., Hong, S.-M., Lim, P., Kamiyama, H., Khan, M., Anders, R. A., … Eshleman, J. R. (2009). KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: implications for the human pancreatic cancer cell of origin. Mol Cancer Res, 7(2), 230–236. https://doi.org/10.1158/1541-7786.MCR-08-0206
Shi, Chanjuan, Seung-Mo Hong, Phillip Lim, Hirohiko Kamiyama, Mehtab Khan, Robert A. Anders, Michael Goggins, Ralph H. Hruban, and James R. Eshleman. “KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: implications for the human pancreatic cancer cell of origin.Mol Cancer Res 7, no. 2 (February 2009): 230–36. https://doi.org/10.1158/1541-7786.MCR-08-0206.
Shi, Chanjuan, et al. “KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: implications for the human pancreatic cancer cell of origin.Mol Cancer Res, vol. 7, no. 2, Feb. 2009, pp. 230–36. Pubmed, doi:10.1158/1541-7786.MCR-08-0206.
Shi C, Hong S-M, Lim P, Kamiyama H, Khan M, Anders RA, Goggins M, Hruban RH, Eshleman JR. KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: implications for the human pancreatic cancer cell of origin. Mol Cancer Res. 2009 Feb;7(2):230–236.

Published In

Mol Cancer Res

DOI

ISSN

1541-7786

Publication Date

February 2009

Volume

7

Issue

2

Start / End Page

230 / 236

Location

United States

Related Subject Headings

  • ras Proteins
  • Stromal Cells
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogene Proteins
  • Polymerase Chain Reaction
  • Pancreatic Neoplasms
  • Pancreas
  • Oncology & Carcinogenesis
  • Mutation
  • Middle Aged