A novel germline BRCA1 mutation identified in a family with hereditary breast and ovarian cancer syndrome.

Pathogenic germline mutations occurring in the BRCA1 (MIM:113705) and BRCA2 (MIM: 600185), which always result in truncated protein or nonsense-mediated mRNA decay, have been identified to increase the risk of hereditary breast, ovarian, pancreatic, prostate, and melanoma cancers. Recent studies show that BRCA1/2 germline mutations also contribute to half of all hereditary breast and ovarian cancer (HBOC). In this case series, we reported a novel frameshift mutation of the BRCA1 gene. This novel frameshift mutation occurs in exon10 of BRCA1 and may result in a lack of the serine cluster domain and BRCA1 C-terminus domain, which mediates the function of BRCA1 in DNA repair and are responsible for activation function of BRCA1. The mutation was present in a Chinese hereditary male/female breast and ovarian cancer family characterized by a high incidence of breast cancer and/or ovarian cancer among the relatives and by a high incidence of triple negative breast cancer (TNBC). Our findings speculate that BRCA1 E1148Rfs*7 mutation may be related to the occurrence of HBOC and even TNBC. Interestingly, three cases of TNBC with this novel BRCA1 mutation in this case series showed a good disease-free survival, one of them has a disease-free survival up to 7 years. Therefore, further study is required to confirm that whether this mutation is associated with good prognosis of HBOC.

MFAP5 promotes basal-like breast cancer progression by activating the EMT program.

PURPOSE: Human basal-like breast cancer (BLBC) is an aggressive malignancy with poor prognosis. Since most current treatments are ineffective, there is an urgent need to identify therapeutic targets for BLBC. Microfibrillar-associated protein 5 (MFAP5) plays an important role in the integration of elastic microfibers and the regulation of endothelial cell behaviors. We previously demonstrated that MFAP5 was significantly overexpressed in BLBC tissues and associated with poor metastasis-free survival of patients with BLBC. However, the detailed role of MFAP5 in BLBC is unclear. Thereby, the current study aimed to investigate the underlying function of MFAP5 in BLBC. METHOD: Functional analyses were conducted for the role of MFAP5 in BLBC in vitro and in vivo. RESULTS: Overexpression of MFAP5 resulted in a significant increase in the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) markers in BLBC in vitro and in vivo. In addition, other metastasis animal models by tail intravenous injection of BT20 cells further confirmed that MFAP5 overexpression promoted BLBC proliferation and BT20 cells metastasis. We found that the TGF-ß or Notch inhibitor significantly reversed the tumorigenicity and metastasis of MFAP5-induced BLBC cells. CONCLUSION: Our findings suggest that MFAP5 may promote EMT in BLBC metastasis via the TGF-ß/Notch pathway.

Characterization of circulating tumor cells in newly diagnosed breast cancer.

Identification of circulating tumor cells (CTCs) by surface marker expression and ploidy analysis [immunostaining-fluorescence in situ hybridization (iFISH)] has been shown to be a highly sensitive method in the identification of certain solid cancers. In the present study, iFISH analysis was performed to identify CTCs in 184 patients with newly diagnosed non-metastatic breast cancer, and the distribution of CTC subtypes was characterized based on cytokeratin (CK) expression and ploidy status. It was revealed that CTCs of non-metastatic, aneuploid breast cancers, independent of CK expression profile, can be detected with high sensitivity (90.76%) by the iFISH system. Higher CTC counts and sensitivity were observed in patients with increased tumor size burden and unfavorable hormone receptor status. Investigation of CTC subtypes based on ploidy analysis indicated that triploid CTCs constituted the majority of CTCs evaluated. While CK-positive CTCs were detected in a small cohort of patients, an overall low rate of CK expression was observed in the 18 patient samples evaluated. Of note, CK expression was rare in CTCs detected in patients with Herceptin 2 (Her2)-positive or triple-negative [estrogen receptor (ER)-, progesterone receptor (PR)- and Her2-negative], indicating that lack of ER and PR may result in promotion of epithelial-mesenchymal transition and enhancement of tumor aggression.