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| |''MET'' | | |''MET'' |
| | ||Missense||The tumorigenic hallmark of HPRCC is ''MET'' germline proto-oncogene mutations, which are often missense, leading to activation of the tyrosine kinase domain of c-MET sans endogenous HGF/SF. The activation subsequently triggers downstream signaling pathways that promote cell survival, proliferation, angiogenesis and inhibition of apoptosis.||Dominant, | | | ||Missense |
| | T3640C (M1149D) |
| | |
| | G3810T (V1206L) |
| | |
| | G3906A (V1238I) |
| | |
| | G3930A (D1246N) |
| | |
| | A3937G (Y1248C) |
| | |The tumorigenic hallmark of HPRCC is ''MET'' germline proto-oncogene mutations, which are often missense, leading to activation of the tyrosine kinase domain of c-MET sans endogenous HGF/SF. The activation subsequently triggers downstream signaling pathways that promote cell survival, proliferation, angiogenesis and inhibition of apoptosis.||Dominant, |
| HPRC is highly penetrant (approaching 100%) | | HPRC is highly penetrant (approaching 100%) |
| | | | | |
| |} | | |} |
| ==Genetic Abnormalities: Somatic== | | ==Genetic Abnormalities: Somatic Mutation Tumor== |
| Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Describe significant second hit mutations, or somatic variants that present as a germline syndrome. In the notes, include details about most common mutations, mechanisms of molecular pathogenesis, alteration-specific prognosis and any other important genetic-related information. Please include references throughout the table. Do not delete the table.'')</span>
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| {| class="wikitable sortable" | | {| class="wikitable sortable" |
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| !Notes | | !Notes |
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| |<span class="blue-text">EXAMPLE:</span> ''BRCA1''||<span class="blue-text">EXAMPLE:</span> Biallelic inactivation variants||<span class="blue-text">EXAMPLE:</span> Second hit mutation can occur as copy neutral LOH, inactivating mutation, deletion, promoter hypermethylation, or a structural abnormality disrupting the gene.|| | | |''MET''||Missense |
| |
| | C3831G (L1213V) |
| |-
| | |
| |<span class="blue-text">EXAMPLE:</span> ''BRCA1''
| | G3930C (D1246H) |
| |<span class="blue-text">EXAMPLE:</span> Reversion mutation
| | |
| |<span class="blue-text">EXAMPLE:</span> After exposure to certain therapies (e.g. PARP inhibitors), a second mutation may restore gene function as a resistance mechanism.
| | T3936C (Y1248H) |
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| |
| | T3997C (M1268D |
| |- | | | ||Somatic |
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| |} | | |} |
| ==Genes and Main Pathways Involved== | | ==Genes and Main Pathways Involved== |
| Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Please include references throughout the table. Do not delete the table.)''</span>
| | Hippo, mTOR or p53 |
| {| class="wikitable sortable" | | {| class="wikitable sortable" |
| |- | | |- |
