Introduction
Methods
Patients and tumours
Immunohistochemical analyses
DNA and RNA extraction
Affymetrix Genome-Wide Human SNP 6.0 Array profiling and analysis of genomic alterations
The Cancer Genome Atlas breast cancer cohort
Quantitative RT-PCR
Classical Sanger sequencing
Whole-exome sequencing
RNA sequencing
Gene expression analysis
Results
IMPC tumours were predominantly pT1N1 ER-positive with high rates of ERBB2 overexpression for T1 tumours
IMPC tumours harboured 17q gain/amplification associated with 6q deletion
SNP start | SNP end | Chr | Cytoband | IMPCs (%) | IDC-NSTs (%) | Genes of interest |
---|---|---|---|---|---|---|
Common regions
| ||||||
Gains | ||||||
36948617 | 146292734 | 8 | p11.23-q24.3 | 60 | 45 | |
Losses | ||||||
113565 | 35436036 | 8 | p23.3-p12 | 63 | 63 | |
46534977 | 90163275 | 16 | q11.2-q24.3 | 55b | 54 | |
6689 | 18896297 | 17 | p13.3-p11.2 | 46 | 43b | |
16055171 | 51219006 | 22 | q11.1-q13.33 | 52 | 40 | |
Specific regions
| ||||||
Gains | ||||||
197811282 | 249198692 | 1 | q31.3-q44 | 23 | 48 | |
52579874 | 67308196 | 17 | q22-q24.3 | 47 | 25 | |
33435161 | 62648208 | 20 | q13.12-q13.33 | 17 | 44 | |
Losses | ||||||
101380020 | 125365648 | 6 | q16.3-q22.31 | 45b | 20 | |
705598 | 13611533 | 18 | p11.32-p11.21 | 15 | 42 | |
28175177 | 35313501 | 18 | q12.1-q12.2 | 24 | 40 | |
Amplifications | ||||||
37097563 | 38618768 | 8 | p11.23-p11.22 | 13 | 26 |
FGFR1, PPAPDC1B, WHSC1L1
|
94967717 | 97023919 | 8 | q22.1 | 21 | 5 |
RAD54B, CCNE2, TP53INP1
|
115849871 | 138121678 | 8 | q23.3-q24.23 | 21 | 14 |
MYC
|
69073647 | 70229171 | 11 | q13.3-q25 | 7 | 22 |
CCND1, ORAOV1, FGF19, FGF4, FGF3
|
37298761 | 38225021 | 17 | q12-q21.1 | 22 | 24 |
STARD3, ERBB2, GRB7
|
57159990 | 62354992 | 17 | q22-q23.3 | 22 | 7 |
BCAS3, TBX2, TLK2, TANC2, PPM1D
|
50695849 | 52586281 | 20 | q13.2 | 15 | 26 |
ZNF217, BCAS1
|
Identification of two different genomic subsets of invasive micropapillary carcinomas
SEC63 and FOXO3genes, localised in 6q minimal region of deletion observed in both genomic groups of IMPCs, downregulation and mutation
Gene | Cases,n | (%) | Chr | Mutation | WH seq | MiSeq | Sanger seq | Effect of the mutation | Type of mutation | PolyPhen-2 score | GERP score | RNA-seq expression |
---|---|---|---|---|---|---|---|---|---|---|---|---|
TP53
| 5 | (10) | 17 | GAA>CAA/p.E286Q | X | NA | X | Missense | Transversion | 1.00 | Yes | |
ATG>ACG/p.M246T | X | NA | X | Missense | Transition | 1.00 | Yes | |||||
GAG>AAG/p.E68K | NA | NA | X | Missense | Transition | 0.09 | ND | |||||
TAC>TGC/p.Y234C | NA | NA | X | Missense | Transition | 0.97 | ND | |||||
c.742_743insA | NA | NA | X | Frame shift | Ins/del | 5.91 | ND | |||||
DNAH9
| 4 | (8) | 17 | A>G | X | X | X | Splice intron | Transition | 4.05 | No coverage | |
CGG>CAG/p.R2605Q | X | X | X | Missense | Transition | 1.00 | No coverage | |||||
ATG>ATA/p.M3430I | NA | X | X | Missense | Transition | 0.00 | ND | |||||
CAG>TAG/p.Q3082* | NA | X | X | Nonsense | Transition | 4.05 | ND | |||||
FBXO38
| 2 | (4) | 5 | TAT>TGT/p.Y1058C | X | X | X | Missense | Transition | 1.00 | Yes | |
GAA>CAA/p.E20Q | NA | X | X | Missense | Transversion | 0.96 | ND | |||||
THSD4
| 2 | (4) | 15 | GAG>AAG/p.E476K | X | X | X | Missense | Transition | 1.00 | Yes | |
GAG>AAG/p.E652K | NA | X | X | Missense | Transition | 0.96 | ND | |||||
TRMT5
| 2 | (4) | 14 | TTT>CTT/p.F303L | X | X | X | Missense | Transition | 0.04 | Yes | |
GAG>CAG/p.E152Q | NA | X | X | Missense | Transversion | 0.03 | ND | |||||
PIK3CA
| 2 | (4) | 3 | CTC>GTC/p.L540V | NA | NA | X | Missense | Transversion | 0.99 | ND | |
CAG>CCG/p.Q546P | NA | NA | X | Missense | Transversion | 1.00 | ND | |||||
FOXO3
| 1 | (2) | 6 | GCA>ACA/p.A267T | NA | NA | X | Missense | Transition | 0.97 | ND | |
CCT>TCT/p.P292S | NA | NA | X | Missense | Transition | 0.34 | ND | |||||
TTG>GTG/p.L528V | NA | NA | X | Missense | Transversion | 0.03 | ND | |||||
BBS12
| 1 | (2) | 4 | CGC>TGC/p.R674C | X | X | X | Missense | Transition | 1.00 | Yes | |
BBS9
| 1 | (2) | 7 | CCA>TCA/p.P77S | X | X | X | Missense | Transition | 1.00 | No coverage | |
CASP8AP2
| 1 | (2) | 6 | GAT>AAT/p.D1420N | X | X | X | Missense | Transition | 1.00 | No coverage | |
EIF2B5
| 1 | (2) | 3 | GCA>ACA/p.A406T | X | * | X | Missense | Transition | 0.05 | Yes | |
FMN2
| 1 | (2) | 1 | GCT>CCT/p.A659P | X | * | * | Missense | Transversion | 0.74 | No coverage | |
HSP90B1
| 1 | (2) | 12 | ACG>ATG/p.T468M | X | X | Missense | Transition | 0.98 | Yes | ||
IKBKE
| 1 | (2) | 1 | GAC>TAC/p.D571Y | X | * | X | Missense | Transversion | 0.68 | Yes | |
PCF11
| 1 | (2) | 11 | AAT>AGT/p.N167S | X | X | X | Missense | Transition | 0.02 | Yes | |
PLCL1
| 1 | (2) | 2 | AAG>AAT/p.K279N | X | X | X | Missense | Transversion | 0.98 | No coverage | |
PTPN21
| 1 | (2) | 14 | CGA>CTA/p.R864L | X | X | X | Missense | Transversion | 1.00 | Yes | |
SEC63
| 1 | (2) | 6 | CGC>TGC/p.R217C | NA | X | X | Missense | Transition | 1.00 | ND | |
SPTLC3
| 1 | (2) | 20 | G>A | X | X | X | Splice intron | Transition | 5.91 | No coverage | |
ST7L
| 1 | (2) | 1 | GAT>GCT/p.D339A | X | X | X | Missense | Transversion | 1.00 | Yes | |
SYNRG
| 1 | (2) | 17 | ATG>ATA/pM970I | X | * | X | Missense | Transition | 0.45 | Yes | |
UBR4
| 1 | (2) | 1 | AAC>AAA/p.N3400K | X | X | X | Missense | Transversion | 0.98 | Yes | |
ZFYVE26
| 1 | (2) | 14 | CAA>CCA/p.Q1582P | X | X | X | Missense | Transversion | 0.00 | Yes |