6 research outputs found

    Whole-exome sequencing reveals critical genes underlying metastasis in oesophageal squamous cell carcinoma

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    Oesophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers, owing to a high frequency of metastasis. However, little is known about the genomic landscape of metastatic ESCC. To identify the genetic alterations that underlie ESCC metastasis, whole-exome sequencing was performed for 41 primary tumours and 15 lymph nodes (LNs) with metastatic ESCCs. Eleven cases included matched primary tumours, synchronous LN metastases, and non-neoplastic mucosa. Approximately 50–76% of the mutations identified in primary tumours appeared in the synchronous LN metastases. Metastatic ESCCs harbour frequent mutations of TP53, KMT2D, ZNF750, and IRF5. Importantly, ZNF750 was recurrently mutated in metastatic ESCC. Combined analysis from current and previous genomic ESCC studies indicated more frequent ZNF750 mutation in diagnosed cases with LN metastasis than in those without metastasis (14% versus 3.4%, n = 629, P = 1.78 × 10–5). The Cancer Genome Atlas data further showed that ZNF750 genetic alterations were associated with early disease relapse. Previous ESCC studies have demonstrated that ZNF750 knockdown strongly promotes proliferation, migration, and invasion. Collectively, these results suggest a role for ZNF750 as a metastasis suppressor. TP53 is highly mutated in ESCC, and missense mutations are associated with poor overall survival, independently of pathological stage, suggesting that these missense mutations have important functional impacts on tumour progression, and are thus likely to be gain-of-function (GOF) mutations. Additionally, mutations of epigenetic regulators, including KMT2D, TET2, and KAT2A, and chromosomal 6p22 and 11q23 deletions of histone variants, which are important for nucleosome assembly, were detected in 80% of LN metastases. Our study highlights the important role of critical genetic events including ZNF750 mutations, TP53 putative GOF mutations and nucleosome disorganization caused by genetic lesions seen with ESCC metastasis.No Full Tex

    Will private general practitioners alter their knowledge, attitude and practice towards counselling and performing cervical smears for their patients?

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    Objective: To investigate if the knowledge, attitude and practice (KAP) on cervical cancer screening of private general practitioners (GPs) can be modified by education. Design: A controlled cross-over trial of continuing medical education (CME). Subjects: 116 volunteer GPs in private practice who responded to a CME invitation were assigned to study (pap smear workshop, 60) and control (women's health workshop, 56) groups. Sixty-one were randomised while 55 were allocated by date of availability, before knowing which topic occurred on which dates. Main outcome measures: KAP results from self-administrated questionnaires before and 4 months after the workshop. Results: Ninety-four (81% of 116) attended the workshops (46 intervention and 48 controls). Among the 78 doctors (83% of 94) who completed both pre- and post-test questionnaires, while attitude was unchanged, knowledge (in 3 out of 8 items) and behaviour (self-reported Pap smear performing frequency and opportunistic advice for screening) were significantly improved only in the study group. Conclusion: Private GPs acquired more knowledge and reported positive changes in behaviour after an interactive CME workshop. More research is needed in how to maximise the screening capabilities of private GPs and thereby increase the screening rate for cervical cancer in Hong Kong.link_to_subscribed_fulltex

    The immune system and psychiatric disease: a basic science perspective

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