Compendium of Cancer Genome Aberrations

Difference between revisions of "Breast Cancer Table: Recurrent Genomic Alterations Detected by Chromosomal Microarray"

VisualWikitext
[unchecked revision][unchecked revision]
(Created page with "Text")
 
 
(11 intermediate revisions by 2 users not shown)
Line 1: Line 1:
−
Text
+
'''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"
 +
|'''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 [[https://pubmed.ncbi.nlm.nih.gov/32087595/ PMID 32087595]] with permission from Cancer Genetics.
 +
{| class="wikitable"
 +
|'''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
 +
|}
 +
<nowiki>*</nowiki> 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'''
 +
{| class="wikitable"
 +
|'''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 [[https://pubmed.ncbi.nlm.nih.gov/32087595/ PMID 32087595]] with permission from Cancer Genetics.
 +
{| class="wikitable"
 +
|'''Gene'''
 +
|'''Associated Syndrome; Breast Cancer Subtype'''
 +
|-
 +
|''[[ATM]]''
 +
|Ataxia telangiectasia syndrome
 +
|-
 +
|''[[BARD1]]''
 +
|TNBC
 +
|-
 +
|''[[BRCA1]]''
 +
|[[BRCA1 syndrome|BRCA-Related Breast/ Ovarian Cancer Syndrome]]; TNBC
 +
|-
 +
|''[[BRCA2]]''
 +
|[[BRCA2 syndrome|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==
 +
<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

  1. ↑ 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 |pmid= value (help). Check date values in: |date= (help)
Retrieved from "https://ccga.io/index.php?title=Breast_Cancer_Table:_Recurrent_Genomic_Alterations_Detected_by_Chromosomal_Microarray&oldid=10155"