Difference between revisions of "Breast Cancer Table: Recurrent Genomic Alterations Detected by Chromosomal Microarray"
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− | '''Table 1 - Clinically significant copy number alterations in breast cancer''' Table derived from Geiersbach et al., 2018 [ | + | '''Table 1 - Clinically significant copy number alterations and regions of loss of heterozygosity in breast cancer.''' Table derived from Geiersbach et al., 2018 [[https://pubmed.ncbi.nlm.nih.gov/32087595/ PMID 32087595]] with permission from Cancer Genetics.<ref>{{Cite journal|last=Geiersbach|first=Katherine B.|last2=Chen|first2=Hui|last3=Emmadi|first3=Rajyasree|last4=Haskell|first4=Gloria T.|last5=Lu|first5=Xinyan|last6=Liu|first6=Yajuan J.|last7=Swisshelm|first7=Karen|date=2020-06|title=Current concepts in breast cancer genomics: An evidence based review by the CGC breast cancer working group|url=https://pubmed.ncbi.nlm.nih.gov/32087595|journal=Cancer Genetics|volume=244|pages=11–20|doi=10.1016/j.cancergen.2020.02.002|issn=2210-7762|pmid=32087595}}</ref> |
{| class="wikitable" | {| class="wikitable" | ||
|'''Alteration''' | |'''Alteration''' | ||
|'''Relevant Gene(s)''' | |'''Relevant Gene(s)''' | ||
− | |'''CGC Evidence Level''' | + | |'''CGC Evidence Level'''† |
|'''Subgroup Association(s)''' | |'''Subgroup Association(s)''' | ||
|- | |- | ||
Line 12: | Line 12: | ||
|- | |- | ||
|8p11.2 amplification | |8p11.2 amplification | ||
− | |''FGFR1'', ''ZNF703'' | + | |''[[FGFR1]]'', ''[[ZNF703]]'' |
|2 | |2 | ||
|METABRIC IntClust6, ER positive | |METABRIC IntClust6, ER positive | ||
|- | |- | ||
|8q24 amplification | |8q24 amplification | ||
− | |''MYC'' | + | |''[[MYC]]'' |
|2 | |2 | ||
|METABRIC IntClust9, ER positive | |METABRIC IntClust9, ER positive | ||
|- | |- | ||
|9p24 amplification | |9p24 amplification | ||
− | |''JAK2, CD274, PDCD1LG2'' | + | |''[[JAK2]], [[CD274]], [[PDCD1LG2]]'' |
|2 | |2 | ||
|Enriched in TNBC | |Enriched in TNBC | ||
|- | |- | ||
|10q23.3 loss or LOH | |10q23.3 loss or LOH | ||
− | |''PTEN'' | + | |''[[PTEN]]'' |
|2 | |2 | ||
|Enriched in TNBC and in lobular carcinoma | |Enriched in TNBC and in lobular carcinoma | ||
|- | |- | ||
|11q13-q14 gain / amplification | |11q13-q14 gain / amplification | ||
− | |''CCND1'', ''EMS1'', and others | + | |''[[CCND1]]'', ''[[EMS1]]'', and others |
|2 | |2 | ||
|METABRIC IntClust2 | |METABRIC IntClust2 | ||
|- | |- | ||
|16q loss / LOH | |16q loss / LOH | ||
− | |''CDH1'' | + | |''[[CDH1]]'' |
|2 | |2 | ||
|METABRIC IntClust2, ER positive | |METABRIC IntClust2, ER positive | ||
|- | |- | ||
|17p loss / LOH | |17p loss / LOH | ||
− | |''TP53'' | + | |''[[TP53]]'' |
|2 | |2 | ||
|TNBC, basal-like intrinsic subtype | |TNBC, basal-like intrinsic subtype | ||
|- | |- | ||
|17q12 amplification | |17q12 amplification | ||
− | |''ERBB2'' (''HER2'') | + | |''[[ERBB2]]'' (''HER2'') |
|1 | |1 | ||
|METABRIC IntClust5, HER2-enriched | |METABRIC IntClust5, HER2-enriched | ||
|- | |- | ||
|17q21 amplification | |17q21 amplification | ||
− | |''TOP2A'' | + | |''[[TOP2A]]'' |
|2 | |2 | ||
|METABRIC IntClust5, HER2-enriched | |METABRIC IntClust5, HER2-enriched | ||
|- | |- | ||
|17q23 amplification (“17q distal amplicon”) | |17q23 amplification (“17q distal amplicon”) | ||
− | |''RPS6KB'', others | + | |''[[RPS6KB]]'', others |
|2 | |2 | ||
|METABRIC IntClust1 | |METABRIC IntClust1 | ||
|- | |- | ||
|19q12 | |19q12 | ||
− | |''CCNE1'' | + | |''[[CCNE1]]'' |
|2 | |2 | ||
|METABRIC IntClust5; HER2-enriched | |METABRIC IntClust5; HER2-enriched | ||
|- | |- | ||
|20q gain; 20q13 amp | |20q gain; 20q13 amp | ||
− | |''AURKA'', ''GNAS'', ''ZNF217'' | + | |''[[AURKA]]'', ''[[GNAS]]'', ''[[ZNF217]]'' |
|2 | |2 | ||
|METABRIC IntClust1, ER Positive | |METABRIC IntClust1, ER Positive | ||
|} | |} | ||
− | '''Table 2 - Major clinically significant genes associated with somatic sequence alterations in breast cancer''' Table derived from Geiersbach et al., 2018 [ | + | † See table below Table 2 for CGC Evidence levels |
+ | |||
+ | Abbreviations: TNBC, triple negative breast cancer; LOH, loss of heterozygosity. | ||
+ | |||
+ | |||
+ | '''Table 2 - Major clinically significant genes associated with somatic sequence alterations in breast cancer.''' Table derived from Geiersbach et al., 2018 [[https://pubmed.ncbi.nlm.nih.gov/32087595/ PMID 32087595]] with permission from Cancer Genetics. | ||
{| class="wikitable" | {| class="wikitable" | ||
|'''Gene(s)''' | |'''Gene(s)''' | ||
− | |'''CGC Evidence Level''' | + | |'''CGC Evidence Level'''† |
|'''Clinical Significance and Subgroup Association(s)''' | |'''Clinical Significance and Subgroup Association(s)''' | ||
|'''Therapy Implication(s)''' | |'''Therapy Implication(s)''' | ||
|- | |- | ||
− | |''AKT1'' | + | |''[[AKT1]]'' |
|2 | |2 | ||
|Metastatic BC | |Metastatic BC | ||
|AKT inhibitors | |AKT inhibitors | ||
|- | |- | ||
− | |''ATM'' | + | |''[[ATM]]'' |
|1 | |1 | ||
|Possible hereditary risk; TNBC | |Possible hereditary risk; TNBC | ||
|PARP inhibitors (germline) | |PARP inhibitors (germline) | ||
|- | |- | ||
− | |''BRCA1, BRCA2'' | + | |''[[BRCA1]], [[BRCA2]]'' |
|1 | |1 | ||
|Often hereditary risk; TNBC | |Often hereditary risk; TNBC | ||
|Platinum based therapy; PARP inhibitors (germline) | |Platinum based therapy; PARP inhibitors (germline) | ||
|- | |- | ||
− | |''CBFB'' | + | |''[[CBFB]]'' |
|2 | |2 | ||
|ER-positive, Metastatic BC | |ER-positive, Metastatic BC | ||
| | | | ||
|- | |- | ||
− | |''CCND1, CCNE1''* | + | |''[[CCND1]], [[CCNE1]]''* |
|2 | |2 | ||
|HER2-enriched | |HER2-enriched | ||
|CDK4/6 inhibitors | |CDK4/6 inhibitors | ||
|- | |- | ||
− | |''CDK4, CDK6''* | + | |''[[CDK4]], [[CDK6]]''* |
|2 | |2 | ||
|ER-positive, Metastatic BC | |ER-positive, Metastatic BC | ||
|CDK4/6 inhibitors | |CDK4/6 inhibitors | ||
|- | |- | ||
− | |''CDH1'' | + | |''[[CDH1]]'' |
|1 | |1 | ||
|Lobular histology; Possible hereditary risk | |Lobular histology; Possible hereditary risk | ||
| | | | ||
|- | |- | ||
− | |''CDKN2A'' | + | |''[[CDKN2A]]'' |
|2 | |2 | ||
|Metastatic BC | |Metastatic BC | ||
| | | | ||
|- | |- | ||
− | |''CHEK2'' | + | |''[[CHEK2]]'' |
|1 | |1 | ||
|Often hereditary risk | |Often hereditary risk | ||
|PARP inhibitors (germline) | |PARP inhibitors (germline) | ||
|- | |- | ||
− | |''ERBB2''* | + | |''[[ERBB2]]''* |
|1 | |1 | ||
|Rare activating sequence alterations; kinase domain resistance mutations; HER2-enriched | |Rare activating sequence alterations; kinase domain resistance mutations; HER2-enriched | ||
|HER2-targeted therapy | |HER2-targeted therapy | ||
|- | |- | ||
− | |''ESR1'' | + | |''[[ESR1]]'' |
|1 | |1 | ||
|Metastatic ER-positive | |Metastatic ER-positive | ||
|Hormone therapy resistance | |Hormone therapy resistance | ||
|- | |- | ||
− | |''FGFR1 | + | |''[[FGFR1]], [[FGFR2]], [[FGFR3]], [[FGFR4]]'' |
|2 | |2 | ||
|ER-positive | |ER-positive | ||
|FGFR inhibitors | |FGFR inhibitors | ||
|- | |- | ||
− | |''FOXA1'' | + | |''[[FOXA1]]'' |
|2 | |2 | ||
|ER-positive, Luminal subtype, lobular histology | |ER-positive, Luminal subtype, lobular histology | ||
| | | | ||
|- | |- | ||
− | |''GATA3'' | + | |''[[GATA3]]'' |
|2 | |2 | ||
|ER-positive, Luminal subtype | |ER-positive, Luminal subtype | ||
| | | | ||
|- | |- | ||
− | |''JAK2''* | + | |''[[JAK2]]''* |
|2 | |2 | ||
|TNBC | |TNBC | ||
|JAK2 inhibitors, immunotherapy | |JAK2 inhibitors, immunotherapy | ||
|- | |- | ||
− | |''MAP2K4'' | + | |''[[MAP2K4]]'' |
|2 | |2 | ||
|Metastatic BC | |Metastatic BC | ||
| | | | ||
|- | |- | ||
− | |''MAP3K1'' | + | |''[[MAP3K1]]'' |
|2 | |2 | ||
|ER-positive, Metastatic BC | |ER-positive, Metastatic BC | ||
| | | | ||
|- | |- | ||
− | |''MYC''* | + | |''[[MYC]]''* |
|2 | |2 | ||
| | | | ||
| | | | ||
|- | |- | ||
− | |''NBN'' | + | |''[[NBN]]'' |
|1 | |1 | ||
|Possible hereditary risk | |Possible hereditary risk | ||
|PARP inhibitors (germline) | |PARP inhibitors (germline) | ||
|- | |- | ||
− | |''NF1'' | + | |''[[NF1]]'' |
|1 | |1 | ||
|Possible hereditary risk | |Possible hereditary risk | ||
|mTOR/PI3K/AKT inhibitors (germline) | |mTOR/PI3K/AKT inhibitors (germline) | ||
|- | |- | ||
− | |''NTRK1 | + | |''[[NTRK1]], [[NTRK2]], [[NTRK3]]'' |
|1 | |1 | ||
| | | | ||
|NTRK inhibitors | |NTRK inhibitors | ||
|- | |- | ||
− | |''PALB2'' | + | |''[[PALB2]]'' |
|1 | |1 | ||
|Often hereditary risk | |Often hereditary risk | ||
|PARP inhibitors (germline) | |PARP inhibitors (germline) | ||
|- | |- | ||
− | |''PIK3CA'' | + | |''[[PIK3CA]]'' |
|1 | |1 | ||
|ER-Positive, Luminal subtype | |ER-Positive, Luminal subtype | ||
|PI3K inhibitors for selected hotspot mutations; acquired hormone resistance | |PI3K inhibitors for selected hotspot mutations; acquired hormone resistance | ||
|- | |- | ||
− | |''PTEN'' | + | |''[[PTEN]]'' |
|2 | |2 | ||
|Loss in lobular BC | |Loss in lobular BC | ||
Line 200: | Line 205: | ||
|mTOR/PI3K/AKT inhibitors; radiation contraindicated | |mTOR/PI3K/AKT inhibitors; radiation contraindicated | ||
|- | |- | ||
− | |''RB1'' | + | |''[[RB1]]'' |
|2 | |2 | ||
|Metastatic BC | |Metastatic BC | ||
|Acquired hormone resistance | |Acquired hormone resistance | ||
|- | |- | ||
− | |''STK11'' | + | |''[[STK11]]'' |
|1 | |1 | ||
|Possible hereditary risk | |Possible hereditary risk | ||
| | | | ||
|- | |- | ||
− | |''TBX3'' | + | |''[[TBX3]]'' |
|2 | |2 | ||
|Lobular BC | |Lobular BC | ||
| | | | ||
|- | |- | ||
− | |''TOP2A''* | + | |''[[TOP2A]]''* |
|2 | |2 | ||
| | | | ||
|Anthracycline inhibitors | |Anthracycline inhibitors | ||
|- | |- | ||
− | |''TP53'' | + | |''[[TP53]]'' |
|1 | |1 | ||
|TNBC, HER2-enriched, Metastatic BC | |TNBC, HER2-enriched, Metastatic BC | ||
Line 231: | Line 236: | ||
Abbreviations: BC, breast cancer. TNBC, triple negative breast cancer. | Abbreviations: BC, breast cancer. TNBC, triple negative breast cancer. | ||
− | '''Cancer Genomics Consortium Levels of Evidence''' | + | †'''Cancer Genomics Consortium Levels of Evidence''' |
{| class="wikitable" | {| class="wikitable" | ||
|'''Tier''' | |'''Tier''' | ||
Line 253: | Line 258: | ||
|Benign or likely benign | |Benign or likely benign | ||
|} | |} | ||
− | '''Table 3 - Genes with known hereditary risk associations in breast cancer''' Table derived from Geiersbach et al., 2018 [ | + | |
+ | |||
+ | '''Table 3 - Genes with known hereditary risk associations in breast cancer.''' Table derived from Geiersbach et al., 2018 [[https://pubmed.ncbi.nlm.nih.gov/32087595/ PMID 32087595]] with permission from Cancer Genetics. | ||
{| class="wikitable" | {| class="wikitable" | ||
|'''Gene''' | |'''Gene''' | ||
|'''Associated Syndrome; Breast Cancer Subtype''' | |'''Associated Syndrome; Breast Cancer Subtype''' | ||
|- | |- | ||
− | |''ATM'' | + | |''[[ATM]]'' |
|Ataxia telangiectasia syndrome | |Ataxia telangiectasia syndrome | ||
|- | |- | ||
− | |''BARD1'' | + | |''[[BARD1]]'' |
|TNBC | |TNBC | ||
|- | |- | ||
− | |''BRCA1'' | + | |''[[BRCA1]]'' |
− | |BRCA-Related Breast/ Ovarian Cancer Syndrome; TNBC | + | |[[BRCA1 syndrome|BRCA-Related Breast/ Ovarian Cancer Syndrome]]; TNBC |
|- | |- | ||
− | |''BRCA2'' | + | |''[[BRCA2]]'' |
− | |BRCA-Related Breast/ Ovarian Cancer Syndrome; TNBC | + | |[[BRCA2 syndrome|BRCA-Related Breast/ Ovarian Cancer Syndrome]]; TNBC |
|- | |- | ||
− | |''CDH1'' | + | |''[[CDH1]]'' |
|Hereditary Diffuse Gastric Cancer and Lobular Breast Cancer | |Hereditary Diffuse Gastric Cancer and Lobular Breast Cancer | ||
|- | |- | ||
− | |''CHEK2'' | + | |''[[CHEK2]]'' |
|Inherited breast cancer | |Inherited breast cancer | ||
|- | |- | ||
− | |''NBN'' | + | |''[[NBN]]'' |
|Nijmegen Breakage Syndrome | |Nijmegen Breakage Syndrome | ||
|- | |- | ||
− | |''NF1'' | + | |''[[NF1]]'' |
|Neurofibromatosis type 1 | |Neurofibromatosis type 1 | ||
|- | |- | ||
− | |''PALB2'' | + | |''[[PALB2]]'' |
|Fanconi anemia | |Fanconi anemia | ||
|- | |- | ||
− | |''PTEN'' | + | |''[[PTEN]]'' |
|Cowden syndrome | |Cowden syndrome | ||
|- | |- | ||
− | |''RAD51C'' | + | |''[[RAD51C]]'' |
|TNBC | |TNBC | ||
|- | |- | ||
− | |''RAD51D'' | + | |''[[RAD51D]]'' |
|TNBC | |TNBC | ||
|- | |- | ||
− | |''STK11'' | + | |''[[STK11]]'' |
|Peutz-Jeghers syndrome | |Peutz-Jeghers syndrome | ||
|- | |- | ||
− | |''TP53'' | + | |''[[TP53]]'' |
|Li-Fraumeni syndrome | |Li-Fraumeni syndrome | ||
|} | |} | ||
+ | Abbreviations: TNBC, triple negative breast cancer. | ||
+ | ==Reference== | ||
+ | <references /> |
Latest revision as of 17:42, 22 April 2021
Table 1 - Clinically significant copy number alterations and regions of loss of heterozygosity in breast cancer. Table derived from Geiersbach et al., 2018 [PMID 32087595] with permission from Cancer Genetics.[1]
Alteration | Relevant Gene(s) | CGC Evidence Level† | Subgroup Association(s) |
1q gain | unknown | 2 | Most common copy number alteration, often with 16q loss; all subtypes |
8p11.2 amplification | FGFR1, ZNF703 | 2 | METABRIC IntClust6, ER positive |
8q24 amplification | MYC | 2 | METABRIC IntClust9, ER positive |
9p24 amplification | JAK2, CD274, PDCD1LG2 | 2 | Enriched in TNBC |
10q23.3 loss or LOH | PTEN | 2 | Enriched in TNBC and in lobular carcinoma |
11q13-q14 gain / amplification | CCND1, EMS1, and others | 2 | METABRIC IntClust2 |
16q loss / LOH | CDH1 | 2 | METABRIC IntClust2, ER positive |
17p loss / LOH | TP53 | 2 | TNBC, basal-like intrinsic subtype |
17q12 amplification | ERBB2 (HER2) | 1 | METABRIC IntClust5, HER2-enriched |
17q21 amplification | TOP2A | 2 | METABRIC IntClust5, HER2-enriched |
17q23 amplification (“17q distal amplicon”) | RPS6KB, others | 2 | METABRIC IntClust1 |
19q12 | CCNE1 | 2 | METABRIC IntClust5; HER2-enriched |
20q gain; 20q13 amp | AURKA, GNAS, ZNF217 | 2 | METABRIC IntClust1, ER Positive |
† See table below Table 2 for CGC Evidence levels
Abbreviations: TNBC, triple negative breast cancer; LOH, loss of heterozygosity.
Table 2 - Major clinically significant genes associated with somatic sequence alterations in breast cancer. Table derived from Geiersbach et al., 2018 [PMID 32087595] with permission from Cancer Genetics.
Gene(s) | CGC Evidence Level† | Clinical Significance and Subgroup Association(s) | Therapy Implication(s) |
AKT1 | 2 | Metastatic BC | AKT inhibitors |
ATM | 1 | Possible hereditary risk; TNBC | PARP inhibitors (germline) |
BRCA1, BRCA2 | 1 | Often hereditary risk; TNBC | Platinum based therapy; PARP inhibitors (germline) |
CBFB | 2 | ER-positive, Metastatic BC | |
CCND1, CCNE1* | 2 | HER2-enriched | CDK4/6 inhibitors |
CDK4, CDK6* | 2 | ER-positive, Metastatic BC | CDK4/6 inhibitors |
CDH1 | 1 | Lobular histology; Possible hereditary risk | |
CDKN2A | 2 | Metastatic BC | |
CHEK2 | 1 | Often hereditary risk | PARP inhibitors (germline) |
ERBB2* | 1 | Rare activating sequence alterations; kinase domain resistance mutations; HER2-enriched | HER2-targeted therapy |
ESR1 | 1 | Metastatic ER-positive | Hormone therapy resistance |
FGFR1, FGFR2, FGFR3, FGFR4 | 2 | ER-positive | FGFR inhibitors |
FOXA1 | 2 | ER-positive, Luminal subtype, lobular histology | |
GATA3 | 2 | ER-positive, Luminal subtype | |
JAK2* | 2 | TNBC | JAK2 inhibitors, immunotherapy |
MAP2K4 | 2 | Metastatic BC | |
MAP3K1 | 2 | ER-positive, Metastatic BC | |
MYC* | 2 | ||
NBN | 1 | Possible hereditary risk | PARP inhibitors (germline) |
NF1 | 1 | Possible hereditary risk | mTOR/PI3K/AKT inhibitors (germline) |
NTRK1, NTRK2, NTRK3 | 1 | NTRK inhibitors | |
PALB2 | 1 | Often hereditary risk | PARP inhibitors (germline) |
PIK3CA | 1 | ER-Positive, Luminal subtype | PI3K inhibitors for selected hotspot mutations; acquired hormone resistance |
PTEN | 2 | Loss in lobular BC
Possible hereditary risk |
mTOR/PI3K/AKT inhibitors; radiation contraindicated |
RB1 | 2 | Metastatic BC | Acquired hormone resistance |
STK11 | 1 | Possible hereditary risk | |
TBX3 | 2 | Lobular BC | |
TOP2A* | 2 | Anthracycline inhibitors | |
TP53 | 1 | TNBC, HER2-enriched, Metastatic BC
Possible hereditary risk |
Radiation contraindicated |
* Indicates genes more commonly activated by amplification than by sequence variation
Abbreviations: BC, breast cancer. TNBC, triple negative breast cancer.
†Cancer Genomics Consortium Levels of Evidence
Tier | Data Source(s) | Interpretation |
1 | FDA approved therapies, professional guidelines, multiple large clinical studies | Strong evidence supporting clinical utility of variant(s) for diagnosis, selection of therapies, or predicting disease outcome |
2 | One large study or multiple case reports | Emerging evidence supporting clinical utility of variant(s) |
3 | Case reports or expert opinion | Unknown clinical significance |
4 | Published evidence indicating lack of pathogenicity of variant(s) | Benign or likely benign |
Table 3 - Genes with known hereditary risk associations in breast cancer. Table derived from Geiersbach et al., 2018 [PMID 32087595] with permission from Cancer Genetics.
Gene | Associated Syndrome; Breast Cancer Subtype |
ATM | Ataxia telangiectasia syndrome |
BARD1 | TNBC |
BRCA1 | BRCA-Related Breast/ Ovarian Cancer Syndrome; TNBC |
BRCA2 | BRCA-Related Breast/ Ovarian Cancer Syndrome; TNBC |
CDH1 | Hereditary Diffuse Gastric Cancer and Lobular Breast Cancer |
CHEK2 | Inherited breast cancer |
NBN | Nijmegen Breakage Syndrome |
NF1 | Neurofibromatosis type 1 |
PALB2 | Fanconi anemia |
PTEN | Cowden syndrome |
RAD51C | TNBC |
RAD51D | TNBC |
STK11 | Peutz-Jeghers syndrome |
TP53 | Li-Fraumeni syndrome |
Abbreviations: TNBC, triple negative breast cancer.
Reference
- ↑ Geiersbach, Katherine B.; et al. (2020-06). "Current concepts in breast cancer genomics: An evidence based review by the CGC breast cancer working group". Cancer Genetics. 244: 11–20. doi:10.1016/j.cancergen.2020.02.002. ISSN 2210-7762. PMID 32087595 Check
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