title: Alterations of type II classical cadherin, cadherin-10 (CDH10), is associated with pancreatic ductal adenocarcinomas.
abstract: Pancreatic ductal adenocarcinoma (PDAC), either sporadic or familial, has a dismal prognosis and finding candidate genes involved in development of the cancer is crucial for the patient care. First, we identified two patients with germline alterations in or adjacent to CDH10 by chromosome studies and sequencing analyses in 41 familial pancreatic cancer (FPC) cases. One patient had a balanced translocation between chromosome 5 and 20. The breakpoint on chromosome band 5p14.2 was ∼810 Kb upstream of CDH10, while that on chromosome arm 20p was in the pericentromeric region which might result in inactivation of one copy of the gene leading to reduced expression of CDH10. This interpretation was supported by loss of heterozygosity (LOH) seen in this region as determined by short tandem repeat analyses. Another patient had a single nucleotide variant in exon 12 (p.Arg688Gln) of CDH10. This amino acid was conserved among vertebrates and the mutation was predicted to have a pathogenic effect on the protein by several prediction algorithms. Next, we analyzed LOH status in the CDH10 region in sporadic PDAC and at least 24% of tumors had evidence of LOH. Immunohistochemical stains with CDH10 antibody showed a different staining pattern between normal pancreatic ducts and PDAC. Taken together, our data supports the notion that CDH10 is involved in sporadic pancreatic carcinogenesis, and might have a role in rare cases of FPC. Further functional studies are needed to elucidate the tumor suppressive role of CDH10 in pancreatic carcinogenesis.
authors.affiliation: Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.|Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Natini
authors.initials: N
authors.lastname: Jinawath
authors.affiliation: Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Meng-Shin
authors.initials: MS
authors.lastname: Shiao
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Norris
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Murphy
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.|Sidney Kimmel Cancer Center Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Alison P
authors.initials: AP
authors.lastname: Klein
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Raluca
authors.initials: R
authors.lastname: Yonescu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Iacobuzio-Donahue
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Meeker
authors.affiliation: Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Artit
authors.initials: A
authors.lastname: Jinawath
authors.affiliation: Department of Surgery, Jefferson Center for Pancreatic, Biliary and Related Cancers, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.|Sidney Kimmel Cancer Center Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.|Sidney Kimmel Cancer Center Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.affiliation: Department of Surgery, Jefferson Center for Pancreatic, Biliary and Related Cancers, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Brody
authors.affiliation: Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.|Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Sidney Kimmel Cancer Center Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Constance A
authors.initials: CA
authors.lastname: Griffin
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: Shuko
authors.identifier: 0000-0002-5783-2049
authors.initials: S
authors.lastname: Harada
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; C107751:CDH10 protein, human; D015820:Cadherins