G1P3-induced mtROS have a direct role in migratory structure formation and nuclear gene expression to promote breast cancer cell metastasis. Therefore, interrupting mitochondrial functions of G1P3 may improve clinical outcomes in breast cancer patients.

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Introduction: In this study, we sought to further characterize ROS1 protein expression in solid tumors with the complete spectrum of ROS1 genomic alterations. Methods: ROS1 immunohistochemistry (IHC) was performed using the ROS1 (SP384) class I assay per manufacturer's instructions on a variety of solid tumors (n ¼ 32) with known ROS1 genomic alterations. Genomic alterations included fusions (n ¼ 17), gene amplifications (n ¼ 10), and short-variant mutations (n ¼ 11). Results: Of the 32 cases with ROS1 IHC results, 100% (11 of 11) with canonical ROS1 fusions were positive for ROS1 IHC. Among noncanonical ROS1 fusions, only two (of five) cases with SQSTM1-ROS1 and RDX-ROS1 fusions were positive for ROS1 IHC whereas PTPRK-ROS1 (two) and TTC28-ROS1 fusions were negative for ROS1 IHC. One sample with a canonical ROS1 fusion and co-occurring ROS1 resistance mutation (6094G>A, p.G2032R) was positive for ROS1 IHC. A total of 10% (one of 10) of ROS1 amplified tumors were positive for ROS1 IHC. None of the cases (zero of five) with ROS1 short-variant mutations were positive for ROS1 protein expression. Conclusions: These findings suggest that if ROS1 IHC was used as a screening tool for ROS1 fusion, a subset of fusionnegative tumors will reveal positive IHC staining highlighting the value of reflexing to genomic profiling to confirm the presence of a targetable fusion-driver before the initiation of therapy. In addition, the ability of comprehensive genomic profiling to detect ROS1 resistance mutations will be important for clinical decision making.

The State of Punjab has been in focus because of aperceived increasing rate of cancer. Both print and electronic media have created an impression that Punjab, especially the cotton belt of Malwa Region, has become a high incidence cancer region. Actually the increased number of cancer patients might be at least partly because of increasing population and heightened health awareness and reporting. The purpose of this study is to find out the pattern of cancer amongst patients registered in Mukh Mantri Punjab Cancer Rahat Kosh Scheme (MMPCRKS), under cancer registry at Rajindra Hospital Patiala from the various districts of Punjab. The study covers 500 cancer patients registered under MMPCRKS at Rajindra Hospital Patiala, for free cancer treatment. Information regarding age, gender, religion, method of diagnosis and affected sites was obtained. Results were analyzed statistically. Of the 500 patients, 65% were females and 35% were males. The most affected female age groups were 50-54 and 60-64; while males in the age groups of 65-69 and 60-64 had the highest risk. The leading cancers in females were breast followed by cervix and ovary where as in males they were were colon followed by esophagus and tongue. The commonest histological type was adenocarcinoma followed by squamous cell carcinoma. The increasing trend of cancer in Punjab is alarming. Since this study is a preliminary investigation, it could provide a leading role in prevention, treatment and future planning regarding cancer in Punjab.

Centrosome amplification (CA) has been implicated in the progression of various cancer types.Although studies have shown that overexpression of PLK4 promotes CA, the effect of tumor microenvironment on PLK4 regulation is understudied. The aim of this study was to examine the role of hypoxia in promoting CA via PLK4. We found that hypoxia induced CA via HIF-1α. We quantified the prevalence of CA in tumor cell lines and tissue sections from breast cancer (BC), pancreatic adenocarcinoma (PDAC), colorectal cancer (CRC), and prostate cancer (PC) and found that CA was prevalent in cells with increased HIF-1α levels under normoxic conditions. HIF-1α levels were correlated with the extent of CA and PLK4 expression in clinical samples.We analyzed the correlation between PLK4 and HIF1A mRNA levels in The Cancer Genome Atlas (TCGA) datasets to evaluate the role of PLK4 and HIF-1α in BC and PDAC prognosis.High HIF1A and PLK4 levels in BC and PDAC patients were associated with poor overall survival. We confirmed PLK4 as a transcriptional target of HIF-1α and demonstrated that in PLK4 knockdown cells, hypoxia-mimicking agents did not affect CA and expression of CAassociated proteins, underscoring the necessity of PLK4 in HIF-1α-related CA. To further dissect the HIF-1α-PLK4 interplay, we used HIF-1α-deficient cells overexpressing PLK4 and showed a significant increase in CA compared with HIF-1α-deficient cells harboring wild-type PLK4. These findings suggest that HIF-1α induces CA by directly upregulating PLK4 and could help us risk-stratify patients and design new therapies for CA-rich cancers.Implications: Hypoxia drives CA in cancer cells by regulating expression of PLK4, uncovering a novel HIF-1α/ PLK4 axis.

Human papillomavirus-negative (HPV-neg) oropharyngeal squamous cell carcinomas (OPSCCs) are associated with poorer overall survival (OS) compared with HPV-positive (HPV-pos) OPSCCs. The major obstacle in improving outcomes of HPV-neg patients is the lack of robust biomarkers and therapeutic targets. Herein, we investigated the role of centrosome amplification (CA) as a prognostic biomarker in HPV-neg OPSCCs. A quantitative evaluation of CA in clinical specimens of OPSCC revealed that (a) HPV-neg OPSCCs exhibit higher CA compared with HPV-pos OPSCCs, and (b) CA was associated with poor OS, even after adjusting for potentially confounding clinicopathologic variables. Contrastingly, CA was higher in HPV-pos cultured cell lines compared to HPV-neg ones. This divergence in CA phenotypes between clinical specimens and cultured cells can therefore be attributed to an inaccurate recapitulation of the in vivo tumor microenvironment in the cultured cell lines, namely a hypoxic environment. The exposure of HPV-neg OPSCC cultured cells to hypoxia or stabilizing HIF-1α genetically increased CA. Both the 26-gene hypoxia signature as well as the overexpression of HIF-1α positively correlated with increased CA in HPV-neg OPSCCs. In addition, we showed that HIF-1α upregulation is associated with the downregulation of miR-34a, increase in CA and expression of cyclin- D1. Our findings demonstrate that the evaluation of CA may aid in therapeutic decision-making, and CA can serve as a promising therapeutic target for HPV-neg OPSCC patients.

Gliosarcoma is a rare central nervous system (CNS) malignancy. It is characterized by classical biphasic histological pattern with both glial and sarcomatous components, often seen in fifth and sixth decade of life. They are generally located in the supratentorial region. Due to its rarity, exact treatment recommendations are not available in literature. Since it is considered as a variant of glioblastoma multiforme (GBM), it is treated with surgery followed by adjuvant radiotherapy and temozolomide-based chemotherapy. We present a series of four cases of this rare malignancy that were treated at our institute.