title: M6P/IGF2R is mutated in squamous cell carcinoma of the lung.
abstract: In addition to the intracellular sorting of lysosomal enzymes, the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) plays a critical role in regulating the bioavailability of extracellular proteolytic enzymes and growth factors. It has also been shown to be mutated in a number of human cancers, and to suppress cancer cell growth. The purpose of this study was to determine if the M6P/IGF2R is mutated in lung cancer, a leading cause of cancer death worldwide. Archival pathology specimens were obtained on 22 patients with newly diagnosed, untreated squamous cell carcinoma of the lung. Two polymorphisms in the 3'-untranslated region of the M6P/IGF2R were used to screen lung tumors for loss of heterozygosity (LOH) by PCR amplification of DNA. Nineteen of 22 (86%) patients were informative (heterozygous), and 11/19 (58%) squamous cell carcinomas of the lung had LOH at the M6P/IGF2R locus. The remaining allele in 6/11 (55%) LOH patients contained mutations in either the mannose 6-phosphate or the IGF2 binding domain of the M6P/IGF2R. Thus, the M6P/IGF2R is mutated frequently in squamous cell carcinoma of the lung, providing further support for its function as a tumor suppressor.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, NC 27710, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Kong
authors.forename: M S
authors.initials: MS
authors.lastname: Anscher
authors.forename: M K
authors.initials: MK
authors.lastname: Washington
authors.forename: J K
authors.initials: JK
authors.lastname: Killian
authors.forename: R L
authors.initials: RL
authors.lastname: Jirtle
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009154:Mutation; D017527:Receptor, IGF Type 2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D017527:Receptor, IGF Type 2