Genomic landscape of metastatic breast cancer identifies preferentially dysregulated pathways and targets

Paul, Matt R.; Pan, Tien-Chi; Pant, Dhruv K.; Shih, Natalie; Chen, Yan; Harvey, Kyra L.; Solomon, Aaron C.; Lieberman, David; Morrissette, Jennifer J.D.; Soucier-Ernst, Danielle; Goodman, Noah; Stavropoulos, S. William; Maxwell, Kara N.; Clark, Charles C.; Belka, George K.; Feldman, Michael D.; DeMichele, Angela; Chodosh, Lewis A.

doi:10.1172/jci129941

Cited by 79 publications

(96 citation statements)

References 86 publications

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“…related to the progress of human breast cancer [26][27][28][29][30][31]. These data clearly provide useful information for the resistance development of breast cancer.…”

Section: Plos Onementioning

confidence: 72%

Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Shi

Gong

et al. 2020

PLoS ONE

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Breast cancer (BC) is the most frequently diagnosed tumor in women worldwide. Although the combination of surgery and Taxol chemotherapy can achieve a certain therapeutic effect, patients often develop drug-resistance, resulting in a poor prognosis. Therefore, it is significative to seek the molecular mechanism of chemotherapy resistance. Recent studies have found that abnormal epigenetic regulation in breast cells changes the expression of key genes, which can lead to the occurrence, development, and maintenance of cancer, even related to the development of drug-resistance. Therefore, in this study, we performed methylated DNA immunoprecipitation-sequencing (MeDIP-seq) to reveal the difference in methylation between breast cancer drug-resistant cells and sensitive cells. A total of 55076 differentially methylated genes (DMGs) were detected, including 21061 hypermethylated DMGs and 34015 hypomethylated DMGs. Moreover, Gene Ontology (GO) analysis and KEGG pathway analysis reveal the function and pathway of screening genes. These results indicate that DNA methylation may be involved in regulating the occurrence and development of breast cancer.

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“…related to the progress of human breast cancer [26][27][28][29][30][31]. These data clearly provide useful information for the resistance development of breast cancer.…”

Section: Plos Onementioning

confidence: 72%

Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Shi

Gong

et al. 2020

PLoS ONE

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“…Overexpression of R subunit especially RI of PKA is associated with cell proliferation in normal breast, malignant transformation of breast epithelial cells, poor prognosis of breast cancer, and tolerance to anti-estrogen therapy. Recent study demonstrates that nuclear localization of activated PKA is correlated with breast cancer metastasis [ 103 ]. Integrin α9 maintains the stability of β-catenin through ILK/PKA/GSK3 signaling and, thereby promotes the growth and metastasis of triple negative breast cancer cells [ 104 ].…”

Section: The Roles Of Camp–pka–creb Signaling Pathway In Tumorsmentioning

confidence: 99%

Complex roles of cAMP–PKA–CREB signaling in cancer

et al. 2020

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Cyclic adenosine monophosphate (cAMP) is the first discovered second messenger, which plays pivotal roles in cell signaling, and regulates many physiological and pathological processes. cAMP can regulate the transcription of various target genes, mainly through protein kinase A (PKA) and its downstream effectors such as cAMP-responsive element binding protein (CREB). In addition, PKA can phosphorylate many kinases such as Raf, GSK3 and FAK. Aberrant cAMP–PKA signaling is involved in various types of human tumors. Especially, cAMP signaling may have both tumor-suppressive and tumor-promoting roles depending on the tumor types and context. cAMP–PKA signaling can regulate cancer cell growth, migration, invasion and metabolism. This review highlights the important roles of cAMP–PKA–CREB signaling in tumorigenesis. The potential strategies to target this pathway for cancer therapy are also discussed.

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“…S13), but 8p11.21 gain did occur pre-WGD. This gain event and 19p13.3 LOH encompass ANK1 and STK11 genes respectively, both of which have been implicated in tumorigenesis 14,32 , and copy number loss of STK11 has been reported in metastatic breast cancer 33 . Ordering just the HR-/HER2+ subtype, 13q LOH, 14q LOH and 8p11.21 gain occurred as early as the known early drivers (8p LOH and 17p LOH), of which 14q LOH is virtually absent in the White HR-/HER2+ group.…”

Section: Chronological Ordering Of Genomic Aberrationsmentioning

confidence: 88%

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes

Ansari-Pour

Zheng

Pitt

et al. 2020

Preprint

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Black women of African ancestry experience more aggressive breast cancer with higher mortality rates than White women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast tumors, with RNA-seq in a subset, from indigenous African patients in Nigeria in comparison to The Cancer Genome Atlas (n=76) revealed a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations and a 10.5-year younger age at diagnosis. We also found evidence for non-coding mutations in two novel drivers (ZNF217 and SYPL1) and a novel INDEL signature strongly associated with African ancestry proportion. This comprehensive analysis of an understudied population underscores the need to incorporate diversity of genomes as a key parameter in fundamental research with potential to tailor clinical intervention and promote equity in precision oncology care.

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Genomic landscape of metastatic breast cancer identifies preferentially dysregulated pathways and targets

Cited by 79 publications

References 86 publications

Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Complex roles of cAMP–PKA–CREB signaling in cancer

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes

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