Background
Methods
Tumor samples
Sample selection for array expression study
RNA and array expression processing
Array expression analysis
Functional network and pathway analysis
Array copy number variation (CNV) analysis
Immunohistochemistry
Whole exome sequencing (WES)
Mutational analysis
Gene | Forward primer sequence (3′–5′) | Reverse primer sequence (3′–5′) | Product size (bp) |
---|---|---|---|
LOXHD1
| AACACCTATGAGGTTCAGG | GTTGGACTTGTCTGACTTC | 134 |
ERBB4
| AACCTGGAGATAACCAGC | CAAGGCATATCGATCCTC | 169 |
CASP7
| TCGCTTTGGGCTCTTCCA | TGCAGTTACCGTTCCCAC | 213 |
Results
Genes differentially expressed in BCBM vs. BC and prBT
Biofunctional prediction analysis
Category | BCBM vs. BC intersecting with BCBM vs. prBT | BCBM shared with prBT | ||||
---|---|---|---|---|---|---|
p-value | Overlap (%) | Score |
p-value | Overlap (%) | Score | |
Top canonical pathways
| ||||||
Role of BRCA1 in DNA damage response | 1.04E−03 | 7.7 | ||||
d-Myo-inositol (1,4,5,6)-tetrakisphosphate biosynthesis | 4.12E−03 | 5.1 | ||||
d-Myo-inositol (3,4,5,6)-tetrakisphosphate biosynthesis | 4.12E−03 | 5.1 | ||||
Estrogen-mediated S-phase entry | 5.13E−03 | 12.5 | ||||
3-phosphoinositide degradation | 6.98E−03 | 4.7 | ||||
EIF2 signaling | 3.20E−04 | 5.7 | ||||
Systemic lupus erythematosus signaling | 6.10E−03 | 4.8 | ||||
Oxidative phosphorylation | 7.43E−03 | 6.1 | ||||
Superoxide radicals degradation | 7.94E−03 | 25.0 | ||||
TNFR2 signaling | 1.25E−02 | 10.7 | ||||
Top networks related to diseases and functions
| ||||||
Cell cycle, DNA replication, recombination, and repair, cellular assembly and organization | 44 | |||||
Connective tissue disorders, developmental disorder, gastrointestinal disease | 39 | |||||
Cellular assembly and organization, inflammatory disease, inflammatory response | 37 | |||||
Cancer, cell death and survival, organismal injury and abnormalities | 51 | |||||
Hereditary disorder, neurological disease, organismal injury and abnormalities | 48 | |||||
Carbohydrate metabolism, drug metabolism, molecular transport | 41 |
Genes and biofunctions shared between BCBM and prBT
Array CNV analysis
Case | Copy number state | No. of OMIM genes1
| Important cancer genes | Array nomenclature2
|
---|---|---|---|---|
Jed81_MT | Mosaic-loss | 226 |
TP53
| arr[hg19] 17p13.3p11.2(525-20,011,122)x1-2 |
Jed82_MT | Mosaic-loss | 291 |
TP53
| arr[hg19] 17p13.3q12(525-32,273,420)x1-2 |
Jed89_MT | Mosaic-loss | 289 |
TP53
| arr[hg19] 17p13.3q11.2(525-31,245,235)x1-2 |
Jed82_MT | Loss | 6 |
BRCA1
| arr[hg19] 17q21.31(41,251,930-41,829,105)x1 |
Jed81_MT | Gain | 5 |
BRCA2
| arr[hg19] 13q13.1q13.2(32,960,791-34,576,864)x3 |
Jed89_MT | Mosaic-loss | 103 |
BRCA2
| arr[hg19] 13q11q14.2(19,436,286-47,693,486)x1-2 |
Jed82_MT | Gain | 23 |
ERBB2
| arr[hg19] 17q12q21.1(37,063,504-38,179,492)x4 |
Jed81_MT | Mosaic-loss | 435 |
IDH1
| arr[hg19] 2q14.3q37.3(123,839,696-242,275,944)x1-2 |
Jed82_MT | Mosaic-loss | 75 |
IDH1
| arr[hg19] 2q32.3q35(192,641,695-216,741,600)x1-2 |
Jed89_MT | Gain | 11 |
IDH2
| arr[hg19] 15q26.1(90,592,464-91,543,761)x4 |
Immunohistochemistry
Whole exome sequencing
Jed81_MT1,2
| Jed82_MT1,2
| Jed89_MT1,2
| Gene | Read depth | Consequence | HGVSc3
| HGVSp4
|
---|---|---|---|---|---|---|---|
he |
ANLN
| 11 | Inframe insertion | NM_018685.2:c.881_884delCTTCinsCTTCTTC | NM_018685.2:c.881_884delCTTCinsCTTCTTC | ||
he |
BCL9L
| 19 | Missense | NM_182557.2:c.1276G > C | NP_872363.1:p.Glu426Gln | ||
he | ho |
CASP7
| 18 | Frameshift | NM_001267057.1:c.128_130delTTTinsT | NP_001253986.1:p.Leu44SerfsTer70 | |
he |
CDH1
| 26 | Missense | NM_004360.3:c.1198G > C | NP_004351.1:p.Asp400His | ||
he |
CDH9
| 33 | Missense | NM_016279.3:c.643G > T | NP_057363.3:p.Gly215Cys | ||
he |
CDH10
| 128 | Missense | NM_006727.3:c.1708G > C | NP_006718.2:p.Asp570His | ||
ho | ho | ho |
CYFIP2
| 12, 26, 16 | Frameshift | NM_001037333.1:c.280_281delCCinsCCC | NP_001032410.1:p.Gln95ProfsTer15 |
he |
DAPK1
| 19 | Missense | NM_004938.2:c.3090G > T | NP_004929.2:p.Gln1030His | ||
he |
E2F7
| 16 | Missense | NM_203394.2:c.1292C > T | NP_976328.2:p.Pro431Leu | ||
he |
ERRB4
| 24 | Missense | NM_005235.2:c.257A > T | NP_005226.1:p.Tyr86Phe | ||
he |
ERRB4
| 31 | Missense | NM_005235.2:c.2621A > T | NP_005226.1:p.Glu874Val | ||
he |
FLT3
| 14 | Missense | NM_004119.2:c.2957C > T | NP_004110.2:p.Pro986Leu | ||
ho |
FOXD4
| 50 | Frameshift | NM_207305.4:c.1264_1271delGTTTTTTTinsGTTTTTTTT | NP_997188.2:p.Leu424PhefsTer59 | ||
ho |
FOXD4
| 13 | Frameshift | NM_207305.4:c.755_756delGGinsGGG | NP_997188.2:p.Arg253GlufsTer230 | ||
he |
FOXD4L1
| 74 | Frameshift | NM_012184.4:c.763_764delGGinsGGG | NP_036316.1:p.Arg256GlufsTer72 | ||
ho |
HEPACAM
| 24 | Stop gained | NM_152722.4:c.298C > T | NP_689935.2:p.Arg100Ter | ||
he |
IDH3G
| 15 | Frameshift | NM_004135.3:c.562_563delAGinsA | NP_004126.1:p.Ser188ThrfsTer2 | ||
he |
LOXHD1
| 27 | Missense | NM_144612.6:c.3124G > A | NP_653213.6:p.Val1042Ile | ||
he |
MAP4K3
| 29 | Stop gained, splice region | NM_003618.3:c.2539G > T | NP_003609.2:p.Glu847Ter | ||
ho | ho |
MMP12
| 27, 19 | Frameshift | NM_002426.4:c.630_631delCAinsAAA | NP_002417.2:p.Thr211AsnfsTer261 | |
he | he |
PIK3C2G
| 24, 14 | Inframe deletion | NM_004570.4:c.384_387delCCCCinsC | NP_004561.3:p.Pro129del | |
he |
PPARG
| 38 | Missense | NM_015869.4:c.1360C > A | NP_056953.2:p.Pro454Thr | ||
he |
RAD54B
| 131 | Frameshift | NM_012415.3:c.2732_2733delAGinsA | NP_036547.1:p.Ter911TyrfsTer16 | ||
he |
RASGRP3
| 20 | Missense | NM_170672.2:c.492G > T | NP_733772.1:p.Glu164Asp |