Breast Cancer: Recurrent Genomic Alterations: Difference between revisions
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|3 | |3 | ||
|Gain of function | |Gain of function | ||
|164040 | |[https://omim.org/entry/164040 164040] | ||
|NPM1 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=NPM1 NPM1] | ||
|NPM1 | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=NPM1&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true NPM1] | ||
|amplification, expression | |amplification, expression | ||
|occurs in ~1% of breast invasive carcinoma, primarily TNBC, mechanism = upregulation of NPM1 expression; poor prognosis, drug resistance in vitro | |occurs in ~1% of breast invasive carcinoma, primarily TNBC, mechanism = upregulation of NPM1 expression; poor prognosis, drug resistance in vitro | ||
|32245950; 30613163 | |[https://pubmed.ncbi.nlm.nih.gov/32245950/ 32245950]; [https://pubmed.ncbi.nlm.nih.gov/30613163/ 30613163] | ||
|- | |- | ||
|''NRAS'' | |''NRAS'' | ||
|3 | |3 | ||
|Gain of function | |Gain of function | ||
|164790 | |[https://omim.org/entry/164790 164790] | ||
|NRAS | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=NRAS NRAS] | ||
|NRAS breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=NRAS&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true NRAS breast] | ||
|amplification, sequence variants | |amplification, sequence variants | ||
|Diseases: metaplastic BC, basal- like or claudin low TNBC | |Diseases: metaplastic BC, basal- like or claudin low TNBC | ||
|29946183;24882719;27628192;24318467 | |[https://pubmed.ncbi.nlm.nih.gov/29946183/ 29946183]; [https://pubmed.ncbi.nlm.nih.gov/24882719/ 24882719]; [https://pubmed.ncbi.nlm.nih.gov/27628192/ 27628192]; [https://pubmed.ncbi.nlm.nih.gov/24318467/ 24318467] | ||
|- | |- | ||
|''NRG1'' | |''NRG1'' | ||
|1 | |1 | ||
|Gain of function | |Gain of function | ||
|142445 | |[https://omim.org/entry/142445 142445] | ||
|NRG1 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=NRG1 NRG1] | ||
|NRG1 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=NRG1&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true NRG1 breast] | ||
|fusion | |fusion | ||
|Therapy: Targetable alteration (FDA-approved therapy for NSCLC and pancreatic cancer). NRG1 encodes multiple isoforms of Nrg1, known as Neuregulin 1 or heregulin, that function as activating ligands for the ErbB3 and ErbB4 receptor tyrosine kinases, causing ERBB3 heterodimerization and downstream signaling of MAPK, PI3K pathways. In addition, NRG1 can function as a tumor suppressor (pro-apoptotic) and some structural rearrangements are inactivating (PMID: 33413557). | |Therapy: Targetable alteration (FDA-approved therapy for NSCLC and pancreatic cancer). NRG1 encodes multiple isoforms of Nrg1, known as Neuregulin 1 or heregulin, that function as activating ligands for the ErbB3 and ErbB4 receptor tyrosine kinases, causing ERBB3 heterodimerization and downstream signaling of MAPK, PI3K pathways. In addition, NRG1 can function as a tumor suppressor (pro-apoptotic) and some structural rearrangements are inactivating (PMID: 33413557). | ||
|29610121; 33413557; 32916265; 39908431 | |[https://pubmed.ncbi.nlm.nih.gov/29610121/ 29610121]; [https://pubmed.ncbi.nlm.nih.gov/33413557/ 33413557]; [https://pubmed.ncbi.nlm.nih.gov/32916265/ 32916265]; [https://pubmed.ncbi.nlm.nih.gov/39908431/ 39908431] | ||
|- | |- | ||
|''NSD1'' | |''NSD1'' | ||
|3 | |3 | ||
|Loss of function | |Loss of function | ||
|606681 | |[https://omim.org/entry/606681 606681] | ||
|NSD1 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=NSD1 NSD1] | ||
|NSD1 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=NSD1&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true NSD1 breast] | ||
|sequence variants | |sequence variants | ||
|occurs in ~1% of breast cancer; essential for anti-estrogen sensitivity to breast cancer; silencing of NSD1 causes resistance to tamoxifen | |occurs in ~1% of breast cancer; essential for anti-estrogen sensitivity to breast cancer; silencing of NSD1 causes resistance to tamoxifen | ||
|21482774; 25611383;34905470 | |[https://pubmed.ncbi.nlm.nih.gov/21482774/ 21482774]; [https://pubmed.ncbi.nlm.nih.gov/25611383/ 25611383]; [https://pubmed.ncbi.nlm.nih.gov/34905470/ 34905470] | ||
|- | |- | ||
|''NTRK1'' | |''NTRK1'' | ||
|1 | |1 | ||
|Gain of function | |Gain of function | ||
|191315 | |[https://omim.org/entry/191315 191315] | ||
|NTRK1 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=NTRK1 NTRK1] | ||
|NTRK1 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=NTRK1&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true NTRK1 breast] | ||
|amplification, sequence variants, fusion | |amplification, sequence variants, fusion | ||
|Therapy: TRK inhibitors for fusions (including pan-Trk inhibitors larotrectinib, entrectinib, and repotrectinib); kinase domain mutations confer resistance to certain TRK inhibitors | |Therapy: TRK inhibitors for fusions (including pan-Trk inhibitors larotrectinib, entrectinib, and repotrectinib); kinase domain mutations confer resistance to certain TRK inhibitors | ||
|29466156; 32348852; 28183697; 30093503; 31838007 | |[https://pubmed.ncbi.nlm.nih.gov/29466156/ 29466156]; [https://pubmed.ncbi.nlm.nih.gov/32348852/ 32348852]; [https://pubmed.ncbi.nlm.nih.gov/28183697/ 28183697]; [https://pubmed.ncbi.nlm.nih.gov/30093503/ 30093503]; [https://pubmed.ncbi.nlm.nih.gov/31838007/ 31838007] | ||
|- | |- | ||
|''NTRK2'' | |''NTRK2'' | ||
|1 | |1 | ||
|Gain of function | |Gain of function | ||
|600456 | |[https://omim.org/entry/600456 600456] | ||
|NTRK2 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=NTRK2 NTRK2] | ||
|NTRK2 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=NTRK2&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true NTRK2 breast] | ||
|amplification, sequence variants, fusion | |amplification, sequence variants, fusion | ||
|Therapy: TRK inhibitors for fusions (including pan-Trk inhibitors larotrectinib, entrectinib, and repotrectinib); kinase domain mutations confer resistance to certain TRK inhibitors | |Therapy: TRK inhibitors for fusions (including pan-Trk inhibitors larotrectinib, entrectinib, and repotrectinib); kinase domain mutations confer resistance to certain TRK inhibitors | ||
|29466156; 28183697; 31838007 | |[https://pubmed.ncbi.nlm.nih.gov/29466156/ 29466156]; [https://pubmed.ncbi.nlm.nih.gov/28183697/ 28183697]; [https://pubmed.ncbi.nlm.nih.gov/31838007/ 31838007] | ||
|- | |- | ||
|''NTRK3'' | |''NTRK3'' | ||
|1 | |1 | ||
|Gain of function | |Gain of function | ||
|191316 | |[https://omim.org/entry/191316 191316] | ||
|NTRK3 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=NTRK3 NTRK3] | ||
|NTRK3 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=NTRK3&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true NTRK3 breast] | ||
|fusion, amplification, sequence variants | |fusion, amplification, sequence variants | ||
|Therapy: TRK inhibitors for fusions (including pan-Trk inhibitors larotrectinib, entrectinib, and repotrectinib); kinase domain mutations confer resistance to certain TRK inhibitors | |Therapy: TRK inhibitors for fusions (including pan-Trk inhibitors larotrectinib, entrectinib, and repotrectinib); kinase domain mutations confer resistance to certain TRK inhibitors | ||
|12450792; 29466156; 28183697; 30093503; 31838007 | |[https://pubmed.ncbi.nlm.nih.gov/12450792/ 12450792]; [https://pubmed.ncbi.nlm.nih.gov/29466156/ 29466156]; [https://pubmed.ncbi.nlm.nih.gov/28183697/ 28183697]; [https://pubmed.ncbi.nlm.nih.gov/30093503/ 30093503]; [https://pubmed.ncbi.nlm.nih.gov/31838007/ 31838007] | ||
|- | |- | ||
|''NUP93'' | |''NUP93'' | ||
|3 | |3 | ||
|Gain of function | |Gain of function | ||
|614351 | |[https://omim.org/entry/614351 614351] | ||
|NUP93 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=NUP93 NUP93] | ||
|NUP93 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=NUP93&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true NUP93 breast] | ||
|amplification, sequence variants, altered expression | |amplification, sequence variants, altered expression | ||
|Diseases: TNBC, claudin-low subtype, alterations are rare. Prognosis: in vitro evidence for association with disease progression in TNBC | |Diseases: TNBC, claudin-low subtype, alterations are rare. Prognosis: in vitro evidence for association with disease progression in TNBC | ||
|27071718; 31959624 | |[https://pubmed.ncbi.nlm.nih.gov/27071718/ 27071718]; [https://pubmed.ncbi.nlm.nih.gov/31959624/ 31959624] | ||
|- | |- | ||
|''PALB2'' | |''PALB2'' | ||
|1 | |1 | ||
|Loss of function | |Loss of function | ||
|610355 | |[https://omim.org/entry/610355 610355] | ||
|PALB2 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PALB2 PALB2] | ||
|PALB2 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=PALB2&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true PALB2 breast] | ||
|sequence variants, other structural rearrangement | |sequence variants, other structural rearrangement | ||
|Diseases: hereditary BC (high penetrance), ovarian cancer risk. HRD. | |Diseases: hereditary BC (high penetrance), ovarian cancer risk. HRD. | ||
|22241545; 24485656; 28319063; 16793542; 30504931; 33247475; 33471991 | |[https://pubmed.ncbi.nlm.nih.gov/22241545/ 22241545]; [https://pubmed.ncbi.nlm.nih.gov/24485656/ 24485656]; [https://pubmed.ncbi.nlm.nih.gov/28319063/ 28319063]; [https://pubmed.ncbi.nlm.nih.gov/16793542/ 16793542]; [https://pubmed.ncbi.nlm.nih.gov/30504931/ 30504931]; [https://pubmed.ncbi.nlm.nih.gov/33247475/ 33247475]; [https://pubmed.ncbi.nlm.nih.gov/33471991/ 33471991] | ||
|- | |- | ||
|''PBRM1'' | |''PBRM1'' | ||
|2 | |2 | ||
|Loss of function | |Loss of function | ||
|606083 | |[https://omim.org/entry/606083 606083] | ||
|PBRM1 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PBRM1 PBRM1] | ||
|PBRM1 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=PBRM1&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true PBRM1 breast] | ||
|sequence variants, other structural rearrangement | |sequence variants, other structural rearrangement | ||
|occurs in ~1-2% of metastatic breast cancer; synthetic lethality with PARP inhibitors, sensitizing for immunotherapy | |occurs in ~1-2% of metastatic breast cancer; synthetic lethality with PARP inhibitors, sensitizing for immunotherapy | ||
|33314633; 33888468; 33004031; 28977912; 26464681 | |[https://pubmed.ncbi.nlm.nih.gov/33314633/ 33314633]; [https://pubmed.ncbi.nlm.nih.gov/33888468/ 33888468]; [https://pubmed.ncbi.nlm.nih.gov/33004031/ 33004031]; [https://pubmed.ncbi.nlm.nih.gov/28977912/ 28977912]; [https://pubmed.ncbi.nlm.nih.gov/26464681/ 26464681] | ||
|- | |- | ||
|''PDCD1LG2'' | |''PDCD1LG2'' | ||
|2 | |2 | ||
|Gain of function | |Gain of function | ||
|605723 | |[https://omim.org/entry/605723 605723] | ||
|PDCD1LG2 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PDCD1LG2 PDCD1LG2] | ||
|PDCD1LG2 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=PDCD1LG2&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true PDCD1LG2 breast] | ||
|amplification | |amplification | ||
|Diseases: enriched in TNBC; Therapy: potential sensitivity to Immune checkpoint inhibitors. PD-L2 (CD273) is the gene product. (part of 9p24.1 amp) | |Diseases: enriched in TNBC; Therapy: potential sensitivity to Immune checkpoint inhibitors. PD-L2 (CD273) is the gene product. (part of 9p24.1 amp) | ||
|26317899; 26541326; 30576871; 34347720 | |[https://pubmed.ncbi.nlm.nih.gov/26317899/ 26317899]; [https://pubmed.ncbi.nlm.nih.gov/26541326/ 26541326]; [https://pubmed.ncbi.nlm.nih.gov/30576871/ 30576871]; [https://pubmed.ncbi.nlm.nih.gov/34347720/ 34347720] | ||
|- | |- | ||
|''PDGFRA'' | |''PDGFRA'' | ||
|3 | |3 | ||
|Gain of function | |Gain of function | ||
|173490 | |[https://omim.org/entry/173490 173490] | ||
|PDGFRA | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PDGFRA PDGFRA] | ||
|PDGFRA breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=PDGFRA&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true PDGFRA breast] | ||
|sequence variants, amplification, other structural rearrangement, fusion | |sequence variants, amplification, other structural rearrangement, fusion | ||
|~1-2% breast carcinoma, associated with mesenchymal type TNBC, emerging therapeutic target, associated with aggressive disease | |~1-2% breast carcinoma, associated with mesenchymal type TNBC, emerging therapeutic target, associated with aggressive disease | ||
|29380207; 23752188; 32152520; 34440080 | |[https://pubmed.ncbi.nlm.nih.gov/29380207/ 29380207]; [https://pubmed.ncbi.nlm.nih.gov/23752188/ 23752188]; [https://pubmed.ncbi.nlm.nih.gov/32152520/ 32152520]; [https://pubmed.ncbi.nlm.nih.gov/34440080/ 34440080] | ||
|- | |- | ||
|''PDGFRB'' | |''PDGFRB'' | ||
|3 | |3 | ||
|Gain of function | |Gain of function | ||
|173410 | |[https://omim.org/entry/173410 173410] | ||
|PDGFRB | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PDGFRB PDGFRB] | ||
|PDGFRB breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=PDGFRB&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true PDGFRB breast] | ||
|amplification, sequence variants | |amplification, sequence variants | ||
|inhibition of tumorigeneisis in BRCA1 deficienct BC cells in preclinical model | |inhibition of tumorigeneisis in BRCA1 deficienct BC cells in preclinical model | ||
|27161491; 22522925; 29380207 | |[https://pubmed.ncbi.nlm.nih.gov/27161491/ 27161491]; [https://pubmed.ncbi.nlm.nih.gov/22522925/ 22522925]; [https://pubmed.ncbi.nlm.nih.gov/29380207/ 29380207] | ||
|- | |- | ||
|''PGR'' | |''PGR'' | ||
|2 | |2 | ||
|Gain of function | |Gain of function | ||
|607311 | |[https://omim.org/entry/607311 607311] | ||
|PGR | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PGR PGR] | ||
|PGR breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=PGR&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true PGR breast] | ||
|sequence variants, altered expression | |sequence variants, altered expression | ||
|Diseases: expressed in HR positive breast cancer. Sequence alterations in ligand binding domain (most commonly Y890C) are implicated in hormone resistance (post hormone therapy treatment) | |Diseases: expressed in HR positive breast cancer. Sequence alterations in ligand binding domain (most commonly Y890C) are implicated in hormone resistance (post hormone therapy treatment) | ||
|34057651; 34013318; 31942683; 28532429 | |[https://pubmed.ncbi.nlm.nih.gov/34057651/ 34057651]; [https://pubmed.ncbi.nlm.nih.gov/34013318/ 34013318]; [https://pubmed.ncbi.nlm.nih.gov/31942683/ 31942683]; [https://pubmed.ncbi.nlm.nih.gov/28532429/ 28532429] | ||
|- | |- | ||
|''PIK3CA'' | |''PIK3CA'' | ||
|1 | |1 | ||
|Gain of function | |Gain of function | ||
|171834 | |[https://omim.org/entry/171834 171834] | ||
|PIK3CA | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PIK3CA PIK3CA] | ||
|PIK3CA breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=PIK3CA&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true PIK3CA breast] | ||
|sequence variants | |sequence variants | ||
|Therapy: FDA approved (PI3K inhibitor alpelisib & AKT inhibitor capivasertib); acquired hormone resistance. Diseases: ER-positive BC, including micropapillary, proliferative lesions and invasive cancer precursors. Also in radial scars, codon 1047 most common, 64% overall. Absent in mucinous carcinoma (PMID: 22705004). | |Therapy: FDA approved (PI3K inhibitor alpelisib & AKT inhibitor capivasertib); acquired hormone resistance. Diseases: ER-positive BC, including micropapillary, proliferative lesions and invasive cancer precursors. Also in radial scars, codon 1047 most common, 64% overall. Absent in mucinous carcinoma (PMID: 22705004). | ||
|19418217; 19898424; 23352210; 24186142; 24193002; 30305115; 31091374; 32404150; 35653148; 40454641 | |[https://pubmed.ncbi.nlm.nih.gov/19418217/ 19418217]; [https://pubmed.ncbi.nlm.nih.gov/19898424/ 19898424]; [https://pubmed.ncbi.nlm.nih.gov/23352210/ 23352210]; [https://pubmed.ncbi.nlm.nih.gov/24186142/ 24186142]; [https://pubmed.ncbi.nlm.nih.gov/24193002/ 24193002]; [https://pubmed.ncbi.nlm.nih.gov/30305115/ 30305115]; [https://pubmed.ncbi.nlm.nih.gov/31091374/ 31091374]; [https://pubmed.ncbi.nlm.nih.gov/32404150/ 32404150]; [https://pubmed.ncbi.nlm.nih.gov/35653148/ 35653148]; [https://pubmed.ncbi.nlm.nih.gov/40454641/ 40454641] | ||
|- | |- | ||
|''PIK3R1'' | |''PIK3R1'' | ||
|2 | |2 | ||
|Loss of function | |Loss of function | ||
|171833 | |[https://omim.org/entry/171833 171833] | ||
|PIK3R1 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PIK3R1 PIK3R1] | ||
|PIK3R1 breast | |[https://www.cbioportal.org/results/oncoprint?cancer_study_list=acbc_mskcc_2015%2Cbreast_cptac_gdc%2Cbrca_hta9_htan_2022%2Cbrca_metabric%2Cbreast_msk_2025%2Cbreast_msk_2018%2Cbrca_pareja_msk_2020%2Cbrca_mskcc_2019%2Cbreast_alpelisib_2020%2Cbrca_smc_2018%2Cbrca_bccrc_xenograft_2014%2Cbfn_duke_nus_2015%2Cbrca_bccrc%2Cbrca_broad%2Cbrca_sanger%2Cbrca_tcga_pub2015%2Cbrca_tcga%2Cbrca_tcga_pub%2Cbrca_tcga_pan_can_atlas_2018%2Cbrca_tcga_gdc%2Cbrca_jup_msk_2020%2Cbrca_mapk_hp_msk_2021%2Cmbc_msk_2021%2Cbrca_aurora_2023%2Cbrca_dfci_2020%2Cbrca_igr_2015%2Cbreast_ink4_msk_2021%2Cilc_msk_2023%2Cbrca_cptac_2020%2Cbrca_mbcproject_wagle_2017%2Cbrca_mbcproject_2022%2Cbrca_fuscc_2020&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=mutations%2Cstructural_variants%2Ccna%2Cgistic&case_set_id=all&gene_list=PIK3R1&geneset_list=%20&tab_index=tab_visualize&Action=Submit&exclude_germline_mutations=true PIK3R1 breast] | ||
|sequence variants | |sequence variants | ||
|Diseases: metaplastic BC, basal- like or claudin low TNBC. Loss of function increases PI3K signaling and activates Akt. PI3K/Akt/mTOR inhibitors may be effective (clinical trials ongoing). | |Diseases: metaplastic BC, basal- like or claudin low TNBC. Loss of function increases PI3K signaling and activates Akt. PI3K/Akt/mTOR inhibitors may be effective (clinical trials ongoing). | ||
|29636477; 31209687; 30181556; 34093841; 20212113; 23215720 | |[https://pubmed.ncbi.nlm.nih.gov/29636477/ 29636477]; [https://pubmed.ncbi.nlm.nih.gov/31209687/ 31209687]; [https://pubmed.ncbi.nlm.nih.gov/30181556/ 30181556]; [https://pubmed.ncbi.nlm.nih.gov/34093841/ 34093841]; [https://pubmed.ncbi.nlm.nih.gov/20212113/ 20212113]; [https://pubmed.ncbi.nlm.nih.gov/23215720/ 23215720] | ||
|- | |- | ||
|''PLCG1'' | |''PLCG1'' | ||
|3 | |3 | ||
|Gain of function | |Gain of function | ||
|172420 | |[https://omim.org/entry/172420 172420] | ||
|PLCG1 | |[https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=PLCG1 PLCG1] | ||
|PLCG1 breast | |PLCG1 breast | ||
|sequence variants, amplification, altered expression | |sequence variants, amplification, altered expression | ||