Table I.
Validated chimeric protein fusions and gene truncations in MCF7 and HCC1954 breast cancer cell lines.
Cell line | Genomic changes | Chromosome locations | Genes affected | Effect on coding | Somatic changes reported in cancers | Validation method |
---|---|---|---|---|---|---|
MCF7 | Inter-chromosomal translocation | t(17;20)(q23.2;q13.13) | BCAS3 and BCAS4 | chimeric protein | Fusion is recurrently present in MCF7 breast and HCT116 colon cancer cell lines. | cDNA, genomic and published [9, 20, 28, 32, 53] |
MCF7 | Inter-chromosomal translocation | t(17;3)(q22;p14.1) | RAD51C.2 and ATXN7 | chimeric protein | Decreased expression of RAD51C found in majority of breast cancer cell lines. | FISH, cDNA, genomic and published [28, 32] |
MCF7 | Intra-chromosomal inversion | t(20;20)(q13.13;q13.13) | SULF2 and ARFGEF2 | chimeric protein | SULF2 is a known tumor suppressor. SULF2 siRNA silencing is tumorigenic in vivo. | cDNA, genomic and published [9, 28, 32] |
MCF7 | Inter-chromosomal translocation | t(3;20)(p14.1;q13.13) | SULF2 and PRICKLE2 | chimeric protein | see above SULF2 function and phenotype | Genomic and published [9, 28, 32] |
MCF7 | Intra-chromosomal indel | t(19;19)(p13.11;p13.11) | MYO9B and FCHO1 | chimeric protein | MYO9B mutations associate with different inflammatory or autoimmune diseases. | Genomic and published [9, 32] |
MCF7 | Intra-chromosomal indel | t(17;17)(q22;q23.1) | BC017255 and TMEM49 | chimeric protein | High-level amplification at TMEM49 induces high expression of miR-21, which targets PTEN and results in an aggressive breast cancer phenotype. [54] | Genomic and published [9] |
MCF7 | Intra-chromosomal inversion | t(17;17)(q23.1;q23.1) | RPS6KB1 and TMEM49 | chimeric protein | See above TMEM49 function and phenotype. RPS6KB1 is amplified and overexpressed in 10–30% of primary breast cancers and cell lines. RPS6KB1 is regulated by the mTOR pathway which regulates cell cycle, growth and survival. [55] | Genomic and published [9, 32] |
MCF7 | Intra-chromosomal inversion | t(5;5)(q12.1;q12.1) | DEPDC1B and ELOVL7 | chimeric protein | ELOVL7 is over expressed in bladder, breast, colorectal, esophageal, gastric, and prostate cancers. High-fat diet promotes growth of in vivo tumors of ELOVL7-expressed prostate cancer. [56] | cDNA, genomic and published [9, 28, 32] |
MCF7 | Inter-chromosomal translocation | t(3;17)(p14.2;q22) | TEX14 and PTPRG | chimeric protein | PTPRG is a known tumor suppressor in kidney, lung and breast cancers. PTPRG has been shown to inhibit MCF7 anchorage-independent growth and reduce estrogenic response cell proliferation. [57] | Genomic and published [9, 32] |
MCF7 | Inter-chromosomal translocation | t(17;20)(q24.3;q13.32) | ABCA5 and PPP4R1L | chimeric protein | Induction of ABCA5 correlates with differentiation state of human colon tumor. | Genomic and published [9] |
MCF7 | Intra-chromosomal inversion | t(X;X)(p22.2;p22.2) | CXorf15 and SYAP1 | chimeric protein | no known cancer phenotype | Genomic and published [9, 32] |
MCF7 | Inter-chromosomal translocation | t(3;17)(p14.1;q23.2) | BRIP1 | truncation | BRIP1 truncations confer a two-fold increased risk of developing breast cancer. Truncation mutants block double stranded break repair. | Genomic and published [9] |
HCC1954 | Inter-chromosomal translocation | t(5;8)(q23.1;q13.13) | EIF3E | truncation | Truncation is tumorigenic in vivo. Decreased expression found in one third of all human breast carcinomas. | cDNA, genomic and published [12, 33] |
HCC1954 | Inter-chromosomal translocation | t(5;8)(q35.3;q24.21) | NSD1 | truncation | Fusion protein in acute myeloid leukemia. | FISH, cDNA, genomic and published [33] |
HCC1954 | Inter-chromosomal translocation | t(5;8)(p15.33;q24.21) | CLPTM1L and PVT1 | truncation | Amplification of PVT1 linked to pathophysiology of ovarian and breast cancers. | Genomic and published [33] |
HCC1954 | Inter-chromosomal translocation | t(5;8)(p15.35.2;q24.21) | UIMC1 or RAP80 | truncation | Recurrent RAP80 missense mutations identified in breast cancer patients. [45, 46] | Genomic |