Prevalence and spectrum of AKT1, PIK3CA, PTEN and TP53 somatic mutations in Chinese breast cancer patients

Li, Guoli; Guo, Xinwu; Chen, Ming; Tang, Lili; Jiang, Hui; Day, Julia X.; Xie, Yan; Peng, Limin; Xu, Xunxun; Li, Jinliang; Wang, Shouman; Zhi, Xu; Dai, Linjie; Wang, Jun

doi:10.1371/journal.pone.0203495

Cited by 32 publications

(30 citation statements)

References 57 publications

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“…PIK3CA pathway is one of the most frequently deregulated pathways in breast cancer and has been implicated in breast tumor development, progression and therapeutic resistance (26). Somatic mutations in PIK3CA have been demonstrated to be associated with HR-positive (either ER-positive or PRpositive)/HER2−negative breast tumors (26)(27)(28)(29). An increase in PIK3CA mutations have been observed in relapsed breast tumors as compared to primary breast tumors (30).…”

Section: Figure 4 | Correlation Between Clinical and Molecular Featurmentioning

confidence: 99%

Characterizations of Cancer Gene Mutations in Chinese Metastatic Breast Cancer Patients

Tao

Feng

et al. 2020

Front. Oncol.

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Background: Breast cancer (BC) is a type of disease with high heterogeneity. Molecular profiling, by revealing the intrinsic nature of its various subtypes, has extensively improved the therapeutic management of BC patients. However, the genomic mutation landscape of Chinese metastatic BC has not been fully explored. Methods: Matched plasma and mononuclear cells from 290 Chinese women with metastatic BC were sequenced using either of the two commercially-available panels consisting of 520 cancer-related and 108 BC-related genes. Both panels cover the same critical regions of 91 genes. The circulating tumor DNA mutation profile from our cohort was then compared with publicly-available metastatic BC datasets from Memorial Sloan Kettering Cancer Center (MSKCC) and Pan-cancer analysis of whole genomes (PCAWG). Results: A total of 1,201 mutations spanning 91 genes were detected from 234 patients, resulting in a mutation detection rate of 80.7%. TP53 (64.1%) was the gene with highest mutation frequency, followed by PIK3CA (31%), PTEN (11%), and RB1 (10%). Copy number amplifications (CNAs) in MYC (14.1%), FGFR1 (13.3%), CCND1 (6.6%), FGF3 (6.6%), FGF4 (6.2%) and FGF19 (6.2%) were also detected from our cohort. TP53 mutations were significantly more frequent among triple negative BC (TNBC), HR−/HER2+, and HR+/HER2+ BC, while less common in HR+/HER2-(P < 0.01). Meanwhile, PIK3CA mutations were significantly more frequent among HR+/HER2+, HR+/HER2-, and HR−/HER2+ BC, while less common in TNBC (P < 0.01). Pathogenic or likely pathogenic BRCA1/2 germline mutations were detected in 5.9% of the cohort and 4.4% in TNBC subgroup. Maximum allelic fraction (maxAF) of TP53, RB1, and PIK3CA mutations were associated with multiple organ metastasis. Patients with PIK3CA, PTEN, and RB1 mutation were more likely to have liver metastasis (P < 0.02). Compared with MSKCC and PCAWG dataset, Chinese patients had observably difference in genetic variation rates in different molecular subtypes (TNBC: TP53 73.0 vs. 91.

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Section: Figure 4 | Correlation Between Clinical and Molecular Featurmentioning

confidence: 99%

Characterizations of Cancer Gene Mutations in Chinese Metastatic Breast Cancer Patients

Tao

Feng

et al. 2020

Front. Oncol.

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“…The lipid phosphatase activity of the PTEN protein antagonizes the phosphatidylinositol 3‐kinase signaling pathway, while protein phosphatase activity inhibits the MAPK pathway (Weng, Brown, & Eng, 2001a; Weng, Smith, Brown, & Eng, 2001b). Somatic PTEN mutations play an important role in the development of multiple cancer types (Li et al., 2018). However, in 1997, Liaw et al.…”

Section: Discussionmentioning

confidence: 99%

Clinical and molecular aspects of PTEN mutations in 10 pediatric patients

Işık

Şimşir

Solmaz

et al. 2020

Annals of Human Genetics

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Introduction PTEN gene mutations are responsible for the PTEN hamartoma tumor syndrome (PHTS). In this study, clinical and molecular findings of patients carrying PTEN mutations are presented. Our aim is to contribute to genotype–phenotype correlation and define the most common findings of the syndrome in pediatric patients. Methods and Materials Ten molecularly confirmed PHTS patients from seven families were included in the study. All patients were examined by a clinical geneticist. Laboratory test results were obtained from hospital records. Sequencing of PTEN gene was performed. Variant interpretation was done in accordance with 2015 recommendations from the American College of Medical Genetics. Results Macrocephaly was the most common clinical finding, involving all patients. This was followed by skin lesions, neurodevelopmental delay, and pathologic cranial magnetic resonance imaging findings. Seven different heterozygous PTEN gene variants were found in seven families. Four of these were located in exon 5, which has been described as a hot spot area for the PTEN gene. Four mutations were novel. A wide range of phenotypic and genotypic spectra was found in our study group. Conclusion Screening of PTEN mutations in patients with macrocephaly is recommended due to an increased risk of cancer. Further cases are needed to make a phenotype–genotype correlation in PHTS.

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“…In an experiment conducted on men with prostate cancer, it was found that PTEN loss is associated with metastasis and invasion of cancer cells, and undesirable prognosis [ 68 ]. In another experiment in China, on breast cancer patients, occurrence of PTEN mutation is 4.8% [ 69 ]. PTEN can be used as a biomarker for response of patients with cancer into chemotherapy.…”

Section: Pten In Clinical Studiesmentioning

confidence: 99%

PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

et al. 2020

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Cancer is one of the life-threatening disorders that, in spite of excellent advances in medicine and technology, there is no effective cure for. Surgery, chemotherapy, and radiotherapy are extensively applied in cancer therapy, but their efficacy in eradication of cancer cells, suppressing metastasis, and improving overall survival of patients is low. This is due to uncontrolled proliferation of cancer cells and their high migratory ability. Finding molecular pathways involved in malignant behavior of cancer cells can pave the road to effective cancer therapy. In the present review, we focus on phosphatase and tensin homolog (PTEN) signaling as a tumor-suppressor molecular pathway in gastric cancer (GC). PTEN inhibits the PI3K/Akt pathway from interfering with the migration and growth of GC cells. Its activation leads to better survival of patients with GC. Different upstream mediators of PTEN in GC have been identified that can regulate PTEN in suppressing growth and invasion of GC cells, such as microRNAs, long non-coding RNAs, and circular RNAs. It seems that antitumor agents enhance the expression of PTEN in overcoming GC. This review focuses on aforementioned topics to provide a new insight into involvement of PTEN and its downstream and upstream mediators in GC. This will direct further studies for evaluation of novel signaling networks and their targeting for suppressing GC progression.

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Prevalence and spectrum of AKT1, PIK3CA, PTEN and TP53 somatic mutations in Chinese breast cancer patients

Cited by 32 publications

References 57 publications

Characterizations of Cancer Gene Mutations in Chinese Metastatic Breast Cancer Patients

Characterizations of Cancer Gene Mutations in Chinese Metastatic Breast Cancer Patients

Clinical and molecular aspects of PTEN mutations in 10 pediatric patients

PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

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