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rdfs:seeAlso: n8:10.1186%2F1471-2407-6-278 n9:17150109 n10:0 n11:0
bibo:cites: n4:15158434 n4:12846405 n4:11261824 n4:16344724 n4:12860957 n4:12379854 n4:7788735 n4:16299242 n4:10841828 n4:11355950 n4:15118073 n4:15118125 n4:12044528 n4:15457249 n4:16170173 n4:15329413 n4:11582736 n4:7645925
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bibo:doi: 10.1186%2F1471-2407-6-278
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Subject Item: _:vb2009802
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dc:title: methods
n2:contains: _:vb2009804 _:vb2009805 _:vb2009806 _:vb2009803

Subject Item: _:vb2009803
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rdf:value: We subjected those samples to PCR-based semi-automated double stranded nucleotide sequencing, per routine of the Eng lab [>>24<<,25]. Exons 18–21 (exon-intron junctions and flanking intronic regions) of EGFR were amplified using the primers and conditions described by Lynch et al [3] and those of ERBB2 were amplified using the primers and conditions described by
n3:mentions: n4:10841828

Subject Item: _:vb2009804
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rdf:value: We subjected those samples to PCR-based semi-automated double stranded nucleotide sequencing, per routine of the Eng lab [24,>>25<<]. Exons 18–21 (exon-intron junctions and flanking intronic regions) of EGFR were amplified using the primers and conditions described by Lynch et al [3] and those of ERBB2 were amplified using the primers and conditions described by
n3:mentions: n4:12379854

Subject Item: _:vb2009805
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rdf:value: Exons 18–21 (exon-intron junctions and flanking intronic regions) of EGFR were amplified using the primers and conditions described by Lynch et al [>>3<<] and those of ERBB2 were amplified using the primers and conditions described by Stephens et al [6].
n3:mentions: n4:15118073

Subject Item: _:vb2009806
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rdf:value: (exon-intron junctions and flanking intronic regions) of EGFR were amplified using the primers and conditions described by Lynch et al [3] and those of ERBB2 were amplified using the primers and conditions described by Stephens et al [>>6<<]. Double stranded sequencing was performed with the ABI-3700. Mutations or variants were confirmed in both directions as well as confirmed by a second independent PCR reaction.
n3:mentions: n4:15457249

Subject Item: _:vb2009807
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dc:title: background
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Subject Item: _:vb2009808
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rdf:value: These receptors form either homo- or heterodimeric complexes which provides amplification and diversification [>>1<<]. Heterodimerization of the ERBB2 and EGFR is associated with a more robust signaling than homodimerization [2]. Several studies showed that gain-of-function somatic mutations affecting the catalytic domain (specifically the ATP binding
n3:mentions: n4:12860957

Subject Item: _:vb2009809
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rdf:value: the catalytic domain (specifically the ATP binding site, exons 18–21) of EGFR in non-small cell lung carcinomas were strongly associated with response to gefitinib and erlotinib, both related EGFR-tyrosine kinase inhibitors (TKI) [>>3<<-5]. More recently, a number of studies reported the presence of ERBB2 mutations located in the kinase domain (exons 19 and 20) in non-small cell lung carcinomas (NSCLC) that could potentially result in the activation of the tyrosine
n3:mentions: n4:15118073 n4:15329413 n4:15118125

Subject Item: _:vb2009810
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rdf:value: reported the presence of ERBB2 mutations located in the kinase domain (exons 19 and 20) in non-small cell lung carcinomas (NSCLC) that could potentially result in the activation of the tyrosine kinase activity of the receptor protein [>>6<<-9]. In addition to NSCLC, mutations in the ERBB2 kinase domain were described in gastric, colorectal, and breast cancers [10,11].
n3:mentions: n4:12846405 n4:15457249 n4:15158434

Subject Item: _:vb2009811
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rdf:value: In addition to NSCLC, mutations in the ERBB2 kinase domain were described in gastric, colorectal, and breast cancers [>>10<<,11]. In our study, we sought to determine if similar respective gain-of-function EGFR and ERBB2 mutations were present in hepatoma and biliary cancers to determine the potential for ERBB -targeted therapy.
n3:mentions: n4:11355950

Subject Item: _:vb2009812
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rdf:value: In addition to NSCLC, mutations in the ERBB2 kinase domain were described in gastric, colorectal, and breast cancers [10,>>11<<]. In our study, we sought to determine if similar respective gain-of-function EGFR and ERBB2 mutations were present in hepatoma and biliary cancers to determine the potential for ERBB -targeted therapy.
n3:mentions: n4:11261824

Subject Item: _:vb2009813
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rdf:value: Hepatoma is the most common malignant tumor of the liver with a clear rising incidence in the number of cases in the United States, and is largely attributed to the increase in hepatitis C related liver disease [>>12<<]. Cancers of the biliary tract are the second most common primary hepatobiliary cancer [13].
n3:mentions: n4:11582736

Subject Item: _:vb2009814
rdf:type: n3:Context
rdf:value: Cancers of the biliary tract are the second most common primary hepatobiliary cancer [>>13<<]. There is no satisfactory treatment available for patients with hepatobiliary cancers and chemotherapy has been extremely disappointing.
n3:mentions: n4:7788735

Subject Item: _:vb2009815
rdf:type: n3:Context
rdf:value: Studies indicate that EGFR is expressed in up to 85% and 80% of hepatoma and biliary cancers, respectively [>>14<<], and EGF might be required for the growth of those cells [15,16].
n3:mentions: n4:7645925

Subject Item: _:vb2009816
rdf:type: n3:Context
rdf:value: Studies indicate that EGFR is expressed in up to 85% and 80% of hepatoma and biliary cancers, respectively [14], and EGF might be required for the growth of those cells [>>15<<,16]. ERBB2 is also expressed in a significant number of hepatoma and biliary cancers acting as an independent prognostic factor and a major contributor to carcinogenesis [17-21]. Recently, a multi-center phase 2 study looked at the
n3:mentions: n4:11261824

Subject Item: _:vb2009817
rdf:type: n3:Context
rdf:value: Studies indicate that EGFR is expressed in up to 85% and 80% of hepatoma and biliary cancers, respectively [14], and EGF might be required for the growth of those cells [15,>>16<<]. ERBB2 is also expressed in a significant number of hepatoma and biliary cancers acting as an independent prognostic factor and a major contributor to carcinogenesis [17-21]. Recently, a multi-center phase 2 study looked at the efficacy
n3:mentions: n4:12044528

Subject Item: _:vb2009818
rdf:type: n3:Context
rdf:value: ERBB2 is also expressed in a significant number of hepatoma and biliary cancers acting as an independent prognostic factor and a major contributor to carcinogenesis [>>17<<-21]. Recently, a multi-center phase 2 study looked at the efficacy and tolerability of erlotinib in advanced hepatoma and biliary cancers with encouraging results [22,23]. In hepatoma, the reported PFS at 6 months of 32% with disease
n3:mentions: n4:12379854 n4:10841828 n4:16170173 n4:12044528

Subject Item: _:vb2009819
rdf:type: n3:Context
rdf:value: Recently, a multi-center phase 2 study looked at the efficacy and tolerability of erlotinib in advanced hepatoma and biliary cancers with encouraging results [22,>>23<<]. In hepatoma, the reported PFS at 6 months of 32% with disease control (PR + SD) of 59% for a median duration of 4 months. The median overall survival (OS) was 13 months. In biliary cancers, the reported PFS at 6 months was 25% with
n3:mentions: n4:16170173

Subject Item: _:vb2009820
rdf:type: n2:Section
dc:title: discussions and conclusion
n2:contains: _:vb2009821 _:vb2009822

Subject Item: _:vb2009821
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rdf:value: A recently published study showed the lack of somatic mutations in EGFR tyrosine kinase domain in 100 hepatocellular carcinomas confirming our findings [>>26<<]. In contrast, we showed that 11% of hepatocellular carcinomas tested have an ERBB2 mutation occurring in the activation domain. None were found in biliary cancer specimens. Given the availability of agents interfering with ERBB2
n3:mentions: n4:16299242

Subject Item: _:vb2009822
rdf:type: n3:Context
rdf:value: not linked to kinase mutations of EGFR, one single response case was actually linked to a mutation in exon 20 of ERBB2 establishing the potential predictive value of such mutations on responses to agents that target ERBB2 and/or EGFR [>>28<<]. In conclusion, our findings suggest that mutations in the tyrosine kinase domain of ERBB2 in hepatoma may underlie responsiveness to agents that target ERBB2 and/or EGFR.
n3:mentions: n4:16344724

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