scholarly journals High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing.

Author(s):  
Anna Kostecka ◽  
Tomasz Nowikiewicz ◽  
Pawel Olszewski ◽  
Magdalena Koczkowska ◽  
Monika Horbacz ◽  
...  

The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor and peripheral blood from 52 reportedly sporadic breast cancer patients, including breast-conserving surgery cases. Targeted resequencing of 542 cancer associated genes revealed mosaic somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, RB1, NCOR1, MED12, CBFB, TBX3 and TSHR in the normal mammary gland, at considerable allelic frequencies (9x10-2 to 5.2x10-1) indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low level-mosaic (in 10-2 to 10-4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumor mammary gland tissue of breast-conserving surgery patients.

2020 ◽  
Vol 6 (2) ◽  
pp. 16 ◽  
Author(s):  
Yuliya A. Veryaskina ◽  
Sergei E. Titov ◽  
Vlada V. Kometova ◽  
Valerii V. Rodionov ◽  
Igor F. Zhimulev

The purpose of this work is to determine the intratumoral distribution of miRNA expression profiles in luminal breast cancer (BC). The study included 33 certain BC cases of the luminal A or luminal B (Her2-) subtypes. The relative expression levels of miRNA-20a; -21; -125b; -126; -200b; -181a; -205; -221; -222; -451a; -99a; -145; -200a; -214; -30a; -191; and small nuclear RNAs U6, U54, and U58 were measured by RT-qPCR in four intratumor areas in each of 33 luminal BC specimens and in surrounding normal mammary gland tissues. Comparative analysis of miRNA expression levels between normal mammary gland tissue and different intratumor areas revealed that only four miRNAs (miRNA-21, -200b, -200a, -191) appear as consistently differentiating markers. A comparative analysis of miRNA expression levels between normal mammary gland tissue and the tumor border revealed statistically significant differences for ten miRNAs; 10 miRNAs show differential expression between normal mammary gland tissue and central tumor specimens; 9 miRNAs show differential expression between normal mammary gland tissue and tumor periphery 1; 13 miRNAs show differential expression between normal mammary gland tissue and tumor periphery 2. After comparing the tumor periphery 1 and tumor center, we found statistically significant differences in expression between five miRNAs and after comparing the tumor periphery 2 and tumor center, differences were observed for 12 miRNAs. MiRNA expression levels are subject to considerable variation, depending on the intratumor area. This may explain the inconsistency in miRNA expression estimates in BC coming from different laboratories.


PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258491
Author(s):  
Mamoru Niikura ◽  
Toshiyuki Fukutomi ◽  
Shoichiro Mineo ◽  
Jiro Mitobe ◽  
Fumie Kobayashi

Mastitis is an inflammation of the mammary gland in the breast and is typically due to bacterial infection. In malaria-endemic areas, mastitis with accompanying fever can be challenging to differentiate from malaria. At the same time, it is unclear whether malaria infection is directly involved in the development of mastitis. In the present study, whether mastitis develops during infection with malaria parasites was investigated using a rodent malaria model with Plasmodium berghei (P. berghei; Pb) ANKA. The course of parasitemia in postpartum mice infected with Pb ANKA was similar to the course in infected virgin mice. However, infected postpartum mice died earlier than did infected virgin mice. In addition, the weight of pups from mice infected with Pb ANKA was significantly reduced compared with pups from uninfected mice. The macroscopic and histological analyses showed apparent changes, such as destruction of the alveolus wall and extensive presence of leukocytes, in mammary gland tissue in mice infected during the postpartum period. The findings suggest that women during the postpartum period are more vulnerable to complications when infected with malaria parasites, particularly women who do not acquire protective immunity against malaria parasites. Based on the proteomic analysis, IFN-γ signaling pathway-related proteins in mammary gland tissue of the infected postpartum mice were increased. Our results indicate that inflammation induced by IFN-γ, a proinflammatory cytokine, may contribute to negative histological changes in mammary gland tissue of postpartum mice infected with Pb ANKA. In IFN-γ receptor 1-deficient (IFNGR1-KO) mice, the histological changes in mammary gland tissue of the infected postpartum wild-type mice were improved to almost normal mammary gland structure. Furthermore, weight loss in pups delivered by infected IFNGR1-KO postpartum mice was not observed. Taken together, these findings indicate that inflammation induced by IFN-γ is associated with development of mastitis in postpartum mice infected with Pb ANKA. The present study results may increase our understanding of how disease aggravation occurs during postpartum malaria.


1974 ◽  
Vol 5 (4) ◽  
pp. 337
Author(s):  
K. Murugesan ◽  
S.R. Srivastava ◽  
Kumar A. Sampath ◽  
M.M. Kapur ◽  
K.R. Laumas

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Han Shin Lee ◽  
Hee Jeong Kim ◽  
Il Yong Chung ◽  
Jisun Kim ◽  
Sae Byul Lee ◽  
...  

AbstractWe used 3D printed-breast surgical guides (3DP-BSG) to designate the original tumor area from the pre-treatment magnetic resonance imaging (MRI) during breast-conserving surgery (BCS) in breast cancer patients who received neoadjuvant systemic therapy (NST). Targeting the original tumor area in such patients using conventional localization techniques is difficult. For precise BCS, a method that marks the tumor area found on MRI directly to the breast is needed. In this prospective study, patients were enrolled for BCS after receiving NST. Partial resection was performed using a prone/supine MRI-based 3DP-BSG. Frozen biopsies were analyzed to confirm clear tumor margins. The tumor characteristics, pathologic results, resection margins, and the distance between the tumor and margin were analyzed. Thirty-nine patients were enrolled with 3DP-BSG for BCS. The median nearest distance between the tumor and the resection margin was 3.9 cm (range 1.2–7.8 cm). Frozen sections showed positive margins in 4/39 (10.3%) patients. Three had invasive cancers, and one had carcinoma in situ; all underwent additional resection. Final pathology revealed clear margins. After 3-year surveillance, 3/39 patients had recurrent breast cancer. With 3DP-BSG for BCS in breast cancer patients receiving NST, the original tumor area can be identified and marked directly on the breast, which is useful for surgery. Trial Registration: Clinical Research Information Service (CRIS) Identifier Number: KCT0002272. First registration number and date: No. 1 (27/04/2016).


2021 ◽  
pp. 106378
Author(s):  
Iolly Tábata Oliveira Marques ◽  
Fábio Roger Vasconcelos ◽  
Juliana Paula Martins Alves ◽  
Assis Rubens Montenegro ◽  
César Carneiro Linhares Fernandes ◽  
...  

2020 ◽  
Vol 31 ◽  
pp. S54
Author(s):  
D.G. Tiezzi ◽  
L. de Mattos ◽  
L.F. Orlandini ◽  
F.J. Candido Dos Reis ◽  
H.H. Carrara ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document