title: Novel insulin receptor substrate 1 and 2 variants in breast and colorectal cancer.
abstract: The insulin/insulin-like growth factor pathway is involved in breast and colorectal cancer (CRC) development. In the present study, we analyzed the coding region and short intron-exon borders of the insulin receptor substrate 1 and 2 (IRS‑1 and IRS‑2) genes in 12 cell lines derived from breast cancer (BC), 14 cell lines derived from CRC and 33 primary CRCs. The nucleotide variants identified in BC were 3 in IRS‑1, 1 of which (p.Arg267Cys) was novel and with a pathogenic potential as predicted by in silico analysis and 6 in IRS‑2. Twenty‑one variants in IRS‑1 and 18 in IRS‑2 were identified in the CRC samples. These included 11 novel IRS‑1 variants detected exclusively in CRCs, which included 5 missense (p.Pro559Leu, p.Gln655His, p.Asp1014Gly, p.Asp1181His and pPro1203Ser) with a pathogenic potential as predicted by in silico analysis, 2 frameshifts predicted to generate a truncated protein, 1 splice-site mutation and 3 silent variants. In the CRC samples we also identified 7 novel IRS‑2 variants, including 4 missense variants, which included 2 (p.Asp782Asn and p.Gly1230Ser) with a pathogenic potential as predicted by in silico analysis, 2 frame insertion mutations and 1 silent variant. Most of the novel IRS‑1 and IRS‑2 variants may be involved in the modulation of IRS-1 or IRS‑2 functions and could be relevant to breast and colorectal tumorigenesis.
authors.affiliation: Unit of General Pathology, Aging Research Center, G. d'Annunzio University Foundation, I‑66100 Chieti, Italy. d.esposito@unich.it
authors.forename: Diana Liberata
authors.initials: DL
authors.lastname: Esposito
authors.forename: Fabio
authors.initials: F
authors.lastname: Verginelli
authors.forename: Sonia
authors.initials: S
authors.lastname: Toracchio
authors.forename: Sandra
authors.initials: S
authors.lastname: Mammarella
authors.forename: Laura
authors.initials: L
authors.lastname: De Lellis
authors.forename: Cinzia
authors.initials: C
authors.lastname: Vanni
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Renato
authors.initials: R
authors.lastname: Mariani-Costantini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cama
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D061986:MCF-7 Cells; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D015398:Signal Transduction / Q000235:genetics
chemical_list: C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins