Frequent PIK3CA Mutations in Radial Scars

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.

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Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis

Cancers ◽

10.3390/cancers13133366 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3366

Author(s):

Anna-Sophie Liegmann ◽

Kerstin Heselmeyer-Haddad ◽

Annette Lischka ◽

Daniela Hirsch ◽

Wei-Dong Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Copy Number ◽

Genome Instability ◽

Single Cells ◽

Gene Mutations ◽

Intratumor Heterogeneity ◽

Breast Cancer Patients ◽

Luminal A ◽

Pik3ca Mutations

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification. To further elucidate genomic instability and tumor heterogeneity in older patients, we analyzed the genetic aberration profiles of 39 breast cancer patients aged 50 years and older (median 67 years) with either short (median 2.4 years) or long survival (median 19 years). The analysis was based on copy number enumeration of eight breast cancer-associated genes using multiplex interphase fluorescence in situ hybridization (miFISH) of single cells, and by targeted next-generation sequencing of 563 cancer-related genes. Results: We detected enormous inter- and intratumor heterogeneity, yet maintenance of common cancer gene mutations and breast cancer specific chromosomal gains and losses. The gain of COX2 was most common (72%), followed by MYC (69%); losses were most prevalent for CDH1 (74%) and TP53 (69%). The degree of intratumor heterogeneity did not correlate with disease outcome. Comparing the miFISH results of diploid with aneuploid tumor samples significant differences were found: aneuploid tumors showed significantly higher average signal numbers, copy number alterations (CNAs) and instability indices. Mutations in PIKC3A were mostly restricted to luminal A tumors. Furthermore, a significant co-occurrence of CNAs of DBC2/MYC, HER2/DBC2 and HER2/TP53 and mutual exclusivity of CNAs of HER2 and PIK3CA mutations and CNAs of CCND1 and PIK3CA mutations were revealed. Conclusion: Our results provide a comprehensive picture of genome instability profiles with a large variety of inter- and intratumor heterogeneity in breast cancer patients aged 50 years and older. In most cases, the distribution of chromosomal aneuploidies was consistent with previous results; however, striking exceptions, such as tumors driven by exclusive loss of chromosomes, were identified.

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Influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab or cetuximab as first-line therapy in patients with RAS wild-type metastatic colorectal carcinoma and <3 baseline circulating tumour cells: the randomised phase II VISNÚ-2 study

ESMO Open ◽

10.1016/j.esmoop.2021.100062 ◽

2021 ◽

Vol 6 (2) ◽

pp. 100062

Author(s):

J. Sastre ◽

P. García-Alfonso ◽

J.M. Viéitez ◽

M.T. Cano ◽

F. Rivera ◽

...

Keyword(s):

Colorectal Carcinoma ◽

Phase Ii ◽

Tumour Cells ◽

Circulating Tumour Cells ◽

Wild Type ◽

Metastatic Colorectal Carcinoma ◽

First Line ◽

Pik3ca Mutations ◽

First Line Therapy ◽

Line Therapy

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Screening for PIK3CA mutations among Saudi women with ovarian cancer

Journal of Obstetrics and Gynaecology ◽

10.1080/01443615.2020.1839871 ◽

2021 ◽

pp. 1-7

Author(s):

Wedad Saeed Al-Qahtani ◽

Manal Abduallah Alduwish ◽

Ebtesam M Al-Olayan ◽

Nada Hamad Aljarba ◽

Al-Humaidhi Em ◽

...

Keyword(s):

Ovarian Cancer ◽

Pik3ca Mutations ◽

Saudi Women

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The utility of TP53 and PIK3CA mutations as prognostic biomarkers in salivary adenoid cystic carcinoma

Oral Oncology ◽

10.1016/j.oraloncology.2020.105095 ◽

2021 ◽

Vol 113 ◽

pp. 105095

Author(s):

Helen Adderley ◽

Samuel Rack ◽

Brindley Hapuarachi ◽

Laura Feeney ◽

David Morgan ◽

...

Keyword(s):

Adenoid Cystic Carcinoma ◽

Prognostic Biomarkers ◽

Salivary Adenoid Cystic Carcinoma ◽

Pik3ca Mutations ◽

Adenoid Cystic

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Multigene Combined Detection by RT-qPCR Using Cytological Specimens

Acta Cytologica ◽

10.1159/000514821 ◽

2021 ◽

pp. 1-10

Author(s):

Yang Ma ◽

Jingxia Zhao ◽

Yun Du ◽

Rui Wang ◽

Xiaokun Ji ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Smoking Status ◽

Single Gene ◽

Rna Extraction ◽

Pcr Amplification ◽

Driver Mutations ◽

Amplification Refractory Mutation System ◽

Driver Genes ◽

Mutation Status ◽

Pik3ca Mutations

Objective: The aim of the study was to investigate the mutation status of multiple driver genes by RT-qPCR and their significance in advanced lung adenocarcinoma using cytological specimens. Materials and Methods: 155 cytological specimens that had been diagnosed with lung adenocarcinoma in the Fourth Hospital of Hebei Medical University were selected from April to November 2019. The cytological specimens included serous cavity effusion and fine-needle aspiration biopsies. Among cytological specimens, 108 cases were processed by using the cell block method (CBM), and 47 cases were processed by the disposable membrane cell collector method (MCM) before DNA/RNA extraction. Ten drive genes of EGFR, ALK, ROS1, BRAF, KRAS, NRAS, HER2, RET, PIK3CA, and MET were combined detected at one step by the amplification refractory mutation system and ABI 7500 RT-qPCR. Results: The purity of RNA (p = 0.005) and DNA (p = 0.001) extracted by using the MCM was both significantly higher than that extracted by using the CBM. Forty-seven cases of fresh cell specimens processed by the MCM all succeeded in multigene detections, while of 108 specimens processed by the CBM, 6 cases failed in multigene detections. Among 149 specimens, single-gene mutation rates of EGFR, ALK, ROS1, RET, HER2, MET, KRAS, NRAS, BRAF, and PIK3CA mutations were 57.71%, 6.04%, 3.36%, 2.68%, 2.01%, 2.01%, 1.34%, 0.67%, 0% and 0% respectively, and 6 cases including 2 coexistence mutations. We found that mutation status was correlated with gender (p = 0.047), but not correlated with age (p = 0.141) and smoking status (p = 0.083). We found that the EGFR mutation status was correlated with gender (p = 0.003), age (p = 0.015) and smoking habits (p = 0.007), and ALK mutation status was correlated with age (p = 0.002). Conclusion: Compared with the CBM, the MCM can improve the efficiency of DNA/RNA extraction and PCR amplification by removing impurities and enriching tumor cells. And we speculate that the successful detection rate of fresh cytological specimens was higher than that of paraffin-embedded specimens. EGFR, ALK, and ROS1 mutations were the main driver mutations in patients with advanced lung adenocarcinoma. We speculate that EGFR and ALK are more prone to concomitant mutations, respectively. Targeted therapies for patients with coexisting mutations need further study.

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Lung Adenocarcinoma From East Asian Never-Smokers Is a Disease Largely Defined by Targetable Oncogenic Mutant Kinases

Journal of Clinical Oncology ◽

10.1200/jco.2010.29.6038 ◽

2010 ◽

Vol 28 (30) ◽

pp. 4616-4620 ◽

Cited By ~ 229

Author(s):

Yihua Sun ◽

Yan Ren ◽

Zhaoyuan Fang ◽

Chenguang Li ◽

Rong Fang ◽

...

Keyword(s):

East Asian ◽

Egfr Mutations ◽

Driver Mutations ◽

Single Institution ◽

Pik3ca Mutations ◽

Oncogenic Mutations ◽

Oncogenic Driver ◽

Never Smokers ◽

Lung Adenocarcinomas ◽

Concurrent Analysis

Purpose To determine the proportion of lung adenocarcinomas from East Asian never-smokers who harbor known oncogenic driver mutations. Patients and Methods In this surgical series, 52 resected lung adenocarcinomas from never-smokers (< 100 cigarettes in a lifetime) at a single institution (Fudan University, Shanghai, China) were analyzed concurrently for mutations in EGFR, KRAS, NRAS, HRAS, HER2, BRAF, ALK, PIK3CA, TP53 and LKB1. Results Forty-one tumors harbored EGFR mutations, three harbored EML4-ALK fusions, two harbored HER2 insertions, and one harbored a KRAS mutation. All mutations were mutually exclusive. Thus, 90% (47 of 52; 95% CI, 0.7896 to 0.9625) of lung adenocarcinomas from never-smokers were found to harbor well-known oncogenic mutations in just four genes. No BRAF, NRAS, HRAS, or LKB1 mutations were detected, while 15 had TP53 mutations. Four tumors contained PIK3CA mutations, always together with EGFR mutations. Conclusion To our knowledge, this study represents the first comprehensive and concurrent analysis of major recurrent oncogenic mutations found in a large cohort of lung adenocarcinomas from East Asian never-smokers. Since drugs are now available that target mutant EGFR, HER2, and ALK, respectively, this result indicates that prospective mutation testing in these patients should successfully assign a targeted therapy in the majority of cases.

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