The ATM Gene in Breast Cancer: Its Relevance in Clinical Practice

Stucci, Luigia Stefania; Internò, Valeria; Tucci, Marco; Perrone, Martina; Mannavola, Francesco; Palmirotta, Raffaele; Porta, Camillo

doi:10.3390/genes12050727

Cited by 57 publications

(38 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A few previous studies have analyzed associations between the incidence of ATM variants and the frequency of contralateral breast cancer incidence after radiation therapy 51,52 . These studies suggest that some mutations in ATM may associate with a decreased risk of contralateral breast cancer recurrence 22 . Conversely, several studies have also identified that mutations in ATM may occur with higher frequency in metastatic breast cancer patients 53 .…”

Section: Discussionmentioning

confidence: 89%

“…For instance, somatic inactivation of ATM/CHK2 signaling, through loss of upstream DNA repair pathways, induces resistance to endocrine therapy in ER+/HER2-breast cancer cells and patient tumors [17][18][19] . A role for germline variants in ATM/CHEK2 in ER+/HER2breast cancer initiation and outcomes has also been identified by large and multiple independent epidemiological studies [20][21][22][23] . Mutations in CHEK2 and ATM associate specifically with increased incidence of ER+/HER2-breast cancer that associates with worse survival outcomes 21,22,24 .…”

Section: Introductionmentioning

confidence: 90%

“…A role for germline variants in ATM/CHEK2 in ER+/HER2− breast cancer initiation and outcomes has also been identified by large and multiple independent epidemiological studies 20–23 . Mutations in CHEK2 and ATM associate specifically with increased 21,22,24 incidence of ER+/HER2− breast cancer that associates with worse survival outcomes 21,22,24 . Other studies have independently demonstrated a significant association between high levels of ATM and responsiveness to endocrine therapy 25–27 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness

Şeker

Punturi

Bainbridge

et al. 2020

Preprint

View full text Add to dashboard Cite

Cell cycle checkpoint kinases activated by DNA repair pathways, ATM/Chk2 and ATR/Chk1 are important tumor suppressors. Germline mutations in these genes associate with increased cancer incidence. Specifically, ATM and CHEK2 germline variants associate with the incidence of estrogen receptor (ER)+ breast cancer with poor patient outcome. More recent investigations identified somatic inactivation of ATM/Chk2 as causal to endocrine therapy resistance in ER+ breast cancer patients. However, the relative contributions of germline and somatic inactivation of these cell cycle checkpoint kinases to ER+/HER2- and ER-/PR-/HER2- or triple negative breast cancer (TNBC) incidence and tumor characteristics has not been systematically assessed. Here, we comprehensively compare the association of ATM/CHEK2 and ATR/CHEK1 germline and somatic mutations with age, tumor stage and PR status at diagnosis, and metastatic potential using a meta-dataset compiled from six independent primary and metastatic patient datasets. We observe significantly higher frequency of ATM (*~29.6%) and CHEK2 (9.5%) mutations in metastatic ER+/HER2- breast cancers relative to TNBC (*~11% and 5% respectively)(p=0.03). CHEK2 mutations associate with higher PR positivity, higher tumor stage and younger age at diagnosis for metastatic ER+/HER2- breast cancer patients. These associations are primarily driven by germline, rather than somatic CHEK2 mutations. However, somatic CHEK2 mutations associate with more rapid disease progression on early rounds of endocrine therapy. These results provide the first systematic analysis of the contribution of germline and somatic cell cycle checkpoint kinase mutations to tumor characteristics affecting patient prognosis and treatment outcome. Results of this study suggest more streamlined use of the status of these checkpoint kinases as prognostic and/or predictive biomarkers for ER+/HER2- breast cancer patients.

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness

Şeker

Punturi

Bainbridge

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…While ATM has several tumor suppressing functions, ATM - induced signaling can cause tumor progression via the αvβ3 integrin pathway in some cancers ( 48 ). ATM-dependent signaling in tumor cells can also increase resistance to radiotherapy and chemoresistance ( 49 ). Due to its role in signaling pathways and DNA damage repair, ATM has been proposed as a potential target for the development of future chemotherapies ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

Shared Genetic Risk Factors Between Cancer and Cardiovascular Diseases

Turk

Kunej

2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Cancer and cardiovascular diseases (CVD) account for approximately 27.5 million deaths every year. While they share some common environmental risk factors, their shared genetic risk factors are not yet fully understood. The aim of the present study was to aggregate genetic risk factors associated with the comorbidity of cancer and CVDs. For this purpose, we: (1) created a catalog of genes associated with cancer and CVDs, (2) visualized retrieved data as a gene-disease network, and (3) performed a pathway enrichment analysis. We performed screening of PubMed database for literature reporting genetic risk factors in patients with both cancer and CVD. The gene-disease network was visualized using Cytoscape and the enrichment analysis was conducted using Enrichr software. We manually reviewed the 181 articles fitting the search criteria and included 13 articles in the study. Data visualization revealed a highly interconnected network containing a single subnetwork with 56 nodes and 146 edges. Genes in the network with the highest number of disease interactions were JAK2, TTN, TET2, and ATM. The pathway enrichment analysis revealed that genes included in the study were significantly enriched in DNA damage repair (DDR) pathways, such as homologous recombination. The role of DDR mechanisms in the development of CVDs has been studied in previously published research; however, additional functional studies are required to elucidate their contribution to the pathophysiology to CVDs.

show abstract

“…Ultrasound-guided sampling methods are usually minimally invasive techniques applied to obtain cytological specimens or tissue samples, mainly used for the diagnosis of different types of tumors, such as breast [ 1 ] and prostate cancers [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Ultrasound Guided Sampling Procedures in the Diagnosis of Pelvic Masses: A Narrative Review of the Literature

et al. 2021

View full text Add to dashboard Cite

Ultrasound-guided sampling methods are usually minimally invasive techniques applied to obtain cytological specimens or tissue samples, mainly used for the diagnosis of different types of tumors. The main benefits of ultrasound guidance is its availability. It offers high flexibility in the choice of sampling approach (transabdominal, transvaginal, and transrectal) and short duration of procedure. Ultrasound guided sampling of pelvic masses represents the diagnostic method of choice in selected patients. We carried out a narrative review of literatures regarding the ultrasound-guided methods of cytological and histological evaluation of pelvic masses as well as the positive and negative predictors for the achievement of an adequate sample.

show abstract

The ATM Gene in Breast Cancer: Its Relevance in Clinical Practice

Cited by 57 publications

References 74 publications

Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness

Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness

Shared Genetic Risk Factors Between Cancer and Cardiovascular Diseases

The Role of Ultrasound Guided Sampling Procedures in the Diagnosis of Pelvic Masses: A Narrative Review of the Literature

Contact Info

Product

Resources

About