Gastrointestinal malignancies harbor actionable MET exon 14 deletions
[Paper-level Aggregated] PMCID: PMC4695055
Evidence Type(s): Functional
Summary: Mutation: p.982_1028del47 | Summary: The mutation p.982_1028del47 is associated with the detection of a METex14del transcript, indicating a potential alteration in molecular function related to the MET gene.
Gene→Variant (gene-first): NTRK3(4916):p.982_1028del47
Genes: NTRK3(4916)
Variants: p.982_1028del47
Gastrointestinal malignancies harbor actionable MET exon 14 deletions
[Paper-level Aggregated] PMCID: PMC4695055
Evidence Type(s): Oncogenic
Summary: Mutation: p.982_1028del47 | Summary: The presence of the METex14del mutation (p.982_1028del47) suggests a contribution to tumor development or progression, as it is being screened in a cohort of cancer patients.
Evidence Type: Oncogenic Mutation: T790M | Summary: The T790M mutation is associated with tumor development in the context of non-small cell lung cancer (NSCLC) patients, indicating its role as a somatic variant contributing to cancer progression.
Evidence Type: Oncogenic Mutation: V600E | Summary: The V600E mutation in BRAF is implicated in tumor development, as it was detected in colon cancer cases, suggesting its role as a somatic variant contributing to cancer progression.
Gene→Variant (gene-first): NTRK3(4916):p.982_1028del47 EGFR(1956):T790M BRAF(673):V600E
Genes: NTRK3(4916) EGFR(1956) BRAF(673)
Variants: p.982_1028del47 T790M V600E
A total of 3 out of 42 GC patients were METex14del positive (Table 3). All GC cases were MET IHC 3+ and the only case in the series with MET amplification. For example, one case was a 27-year old male patient who present
[Paragraph-level] PMCID: PMC4695055 Section: RESULTS PassageIndex: 5
Evidence Type(s): Oncogenic
Summary: Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is associated with tumor development in the context of non-small cell lung cancer (NSCLC) patients, indicating its role as a somatic variant contributing to cancer progression. Evidence Type: Oncogenic | Mutation: V600E | Summary: The V600E mutation in BRAF is implicated in tumor development, as it was detected in colon cancer cases, suggesting its role as a somatic variant contributing to cancer progression.
Gene→Variant (gene-first): 1956:T790M 673:V600E
Genes: 1956 673
Variants: T790M V600E
All 13 METex14del cases were further confirmed by qualitative RT-PCR using probes overlapping an exon 13-15 junction, a fusion transcript caused by exon 14 skipping. In all cases, although the absolute Ct (cycles to thre
[Paragraph-level] PMCID: PMC4695055 Section: RESULTS PassageIndex: 4
Evidence Type(s): None
Summary: Not enough information in this passage.
Gene→Variant (gene-first): 7157:c.3082+811A TTTTAACA > GGTTTGAT
Genes: 7157
Variants: c.3082+811A TTTTAACA > GGTTTGAT
The patient cohort from the NEXT-1 trial (NCT02141152), which is an actively enrolling clinical trial for genomic profiling in cancer patients, was used (Figure 1). Of 428 patients enrolled and screened, sufficient RNAs
[Paragraph-level] PMCID: PMC4695055 Section: RESULTS PassageIndex: 2
Evidence Type(s): Functional, Oncogenic
Summary: Evidence Type: Functional | Mutation: p.982_1028del47 | Summary: The mutation p.982_1028del47 is associated with the detection of a METex14del transcript, indicating a potential alteration in molecular function related to the MET gene. Evidence Type: Oncogenic | Mutation: p.982_1028del47 | Summary: The presence of the METex14del mutation (p.982_1028del47) suggests a contribution to tumor development or progression, as it is being screened in a cohort of cancer patients.
Gene→Variant (gene-first): 4916:p.982_1028del47
Genes: 4916
Variants: p.982_1028del47
Gastrointestinal malignancies harbor actionable MET exon 14 deletions
[Paper-level Aggregated] PMCID: PMC4695055
Evidence Type(s): Oncogenic, Functional
Justification: Oncogenic: The presence of the c.3082+811A TTTTAACA > GGTTTGAT mutation in the intron 14 region of the MET gene, along with the confirmation of METex14del cases, suggests a role in cancer development, indicating its potential oncogenic nature. Functional: The mention of qualitative RT-PCR and deep sequencing indicates that the mutation may have functional implications in the context of gene expression and potential alterations in the MET gene's activity.
Gene→Variant (gene-first): TP53(7157):c.3082+811A TTTTAACA > GGTTTGAT
Genes: TP53(7157)
Variants: c.3082+811A TTTTAACA > GGTTTGAT
A total of 3 out of 42 GC patients were METex14del positive (Table 3). All GC cases were MET IHC 3+ and the only case in the series with MET amplification. For example, one case was a 27-year old male patient who present
[Paragraph-level] PMCID: PMC4695055 Section: RESULTS PassageIndex: 5
Evidence Type(s): None
Justification: Not enough information in this passage.
Gene→Variant (gene-first): 1956:T790M 673:V600E
Genes: 1956 673
Variants: T790M V600E
All 13 METex14del cases were further confirmed by qualitative RT-PCR using probes overlapping an exon 13-15 junction, a fusion transcript caused by exon 14 skipping. In all cases, although the absolute Ct (cycles to thre
[Paragraph-level] PMCID: PMC4695055 Section: RESULTS PassageIndex: 4
Evidence Type(s): Diagnostic, Oncogenic
Justification: Diagnostic: The passage indicates that the variant c.3082+811A TTTTAACA > GGTTTGAT is found in all GI cancer samples, suggesting its association with the disease. Oncogenic: The presence of the variant in GI cancer samples implies a potential role in tumor development or progression, as it is discussed in the context of mutations in cancer.
Gene→Variant (gene-first): 7157:c.3082+811A TTTTAACA > GGTTTGAT
Genes: 7157
Variants: c.3082+811A TTTTAACA > GGTTTGAT
The patient cohort from the NEXT-1 trial (NCT02141152), which is an actively enrolling clinical trial for genomic profiling in cancer patients, was used (Figure 1). Of 428 patients enrolled and screened, sufficient RNAs
[Paragraph-level] PMCID: PMC4695055 Section: RESULTS PassageIndex: 2
Evidence Type(s): None
Justification: Not enough information in this passage.
Gene→Variant (gene-first): 4916:p.982_1028del47
Genes: 4916
Variants: p.982_1028del47
A total of 3 out of 42 GC patients were METex14del positive (Table 3). All GC cases were MET IHC 3+ and the only case in the series with MET amplification. For example, one case was a 27-year old male patient who present
[Paragraph-level] PMCID: PMC4695055 Section: RESULTS PassageIndex: 5
Evidence Type(s): None
Justification: Not enough information in this passage.
Gene→Variant (gene-first): 1956:T790M 673:V600E
Genes: 1956 673
Variants: T790M V600E
All 13 METex14del cases were further confirmed by qualitative RT-PCR using probes overlapping an exon 13-15 junction, a fusion transcript caused by exon 14 skipping. In all cases, although the absolute Ct (cycles to thre
[Paragraph-level] PMCID: PMC4695055 Section: RESULTS PassageIndex: 4
Evidence Type(s): Diagnostic, Oncogenic
Justification: Diagnostic: The passage indicates that the variant c.3082+811A TTTTAACA > GGTTTGAT is found in all GI cancer samples, suggesting its association with the disease. Oncogenic: The presence of the variant in GI cancer samples implies a potential role in tumor development or progression, as it is discussed in the context of mutations in cancer.
Gene→Variant (gene-first): 7157:c.3082+811A TTTTAACA > GGTTTGAT
Genes: 7157
Variants: c.3082+811A TTTTAACA > GGTTTGAT
The patient cohort from the NEXT-1 trial (NCT02141152), which is an actively enrolling clinical trial for genomic profiling in cancer patients, was used (Figure 1). Of 428 patients enrolled and screened, sufficient RNAs
[Paragraph-level] PMCID: PMC4695055 Section: RESULTS PassageIndex: 2
Evidence Type(s): None
Justification: Not enough information in this passage.
Gene→Variant (gene-first): 4916:p.982_1028del47
Genes: 4916
Variants: p.982_1028del47