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.
Esposito, D.L., Verginelli, F., Toracchio, S., Mammarella, S., De Lellis, L., Vanni, C., et al. (2013). Novel insulin receptor substrate 1 and 2 variants in breast and colorectal cancer. ONCOLOGY REPORTS, 30(4), 1553-1560 [10.3892/or.2013.2626].
Novel insulin receptor substrate 1 and 2 variants in breast and colorectal cancer
Russo, Antonio;
2013-01-01
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.File | Dimensione | Formato | |
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