title: The stem cell renewal and DNA damage response pathways are frequently altered in fibroepithelial tumors of breast in Indian patients.
abstract: Genetic and epigenetic alterations in genes associated with distinct cellular pathways were checked in fibroepithelial tumors, including fibroadenomas, benign and malignant phyllode and atypical ductal hyperplasia. A panel of 22 genes associated with different cellular pathways such as stem cell renewal (Wnt and Hedgehog), DNA damage response [homologous recombination (HR), mismatch repair (MMR) and nucleotide excision repair (NER)] and cell proliferation signaling pathway were tested. Alterations (genetic/epigenetic) of the genes associated with Wnt signaling pathway were detected in 100% (20/20) of the breast tumors for at least one out of the six Wnt antagonists tested. Frequent molecular alterations (57-64%) were detected in HR and MMR pathway and low frequency of alterations (8-25%) were seen in cell-proliferation and cell signaling pathways showing a differential pattern of alterations in different tumor types. The patterns of alterations, in particular the epigenetic alterations, differed little from that seen previously in breast carcinoma cells, suggesting epigenetic alterations to be an early event in the development of the tumors. In gene ontology analysis, it was evident that Wnt signaling pathway [GO: 0030111, Kegg: 04310], cell proliferation pathway [GO: 0008285] and pathways in cancer [Kegg: 05200] were significantly enriched by differentially altered genes in fibroadenoma and phyllode tumor types. All these results may provide a new breakthrough in early diagnosis, prognosis and treatment of these tumors.
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal 700026, India. Electronic address: nupurmukherjee10@gmail.com.
authors.forename: Nupur
authors.initials: N
authors.lastname: Mukherjee
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal 700026, India. Electronic address: saimulislam80@gmail.com.
authors.forename: Md Saimul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal 700026, India. Electronic address: rittwikab@gmail.com.
authors.forename: Anirban
authors.initials: A
authors.lastname: Roychowdhury
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal 700026, India. Electronic address: anirbanr91@gmail.com.
authors.forename: Rittwika
authors.initials: R
authors.lastname: Bhattacharya
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal 700026, India.
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Chunder
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal 700026, India. Electronic address: bhattacharya.n@gmail.com.
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Bhattacharya
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal 700026, India; Department of Ophthalmology, West Virginia University, Morgantown, WV, United States. Electronic address: satyabratasinha@gmail.com.
authors.forename: Satyabrata
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, India. Electronic address: nalam@cnci.org.in.
authors.forename: Neyaz
authors.initials: N
authors.lastname: Alam
authors.affiliation: Department of Pathology, Sushruta Nagar, Darjeeling, West Bengal, India. Electronic address: anuproy99@yahoo.com.
authors.forename: Anup
authors.initials: A
authors.lastname: Roy
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India. Electronic address: susantarc@gmail.com.
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, West Bengal 700026, India. Electronic address: ckpanda.cnci@gmail.com.
authors.forename: Chinmay Kumar
authors.initials: CK
authors.lastname: Panda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D000066673:Cell Self Renewal; D004249:DNA Damage / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D042282:Microdissection; D008875:Middle Aged; D018225:Neoplasms, Fibroepithelial / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology*; D012150:Polymorphism, Restriction Fragment Length; D015398:Signal Transduction / Q000502:physiology*; D055815:Young Adult
keywords: Cell cycle regulation; DNA damage response pathway; Fibroepithelial tumors; Genetic/epigenetic alterations; Stem cell renewal pathway