A Novel Oncogenic Driver in a Lung Adenocarcinoma Patient Harboring an EGFR-KDD and Response to Afatinib.

Introduction: Oncogenic mutations in the epidermal growth factor receptor (EGFR) occur frequently in patients with lung cancer. These mutations may serve as critical predictive biomarkers in patients with non-small cell lung cancer (NSCLC). Among them, EGFR exon 18-25 kinase domain duplication (EGFR-KDD) mutations have been identified as a novel EGFR gene subtype in NSCLC. Case Presentation: We reported a rare case of a 59-year-old male diagnosed with adenocarcinoma. A biopsy revealed an EGFR-KDD identified by the next generation sequencing (NGS). Effective treatment outcome has been observed after administration with afatinib. Conclusion: This case highlights that comprehensive NGS technique is valuable in detecting novel genetic mutations in tumors.

Study on phototherapeutic keratotomy for bacterial corneal lesions in rabbit / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the effect of phototherapeutic keratectomy (PTK) on rabbit bacterial corneal ulcer model and explore the clinical potential of this method. METHODS:Totally 48 eyes from all the 24 New Zealand rabbits were inoculated with Staphylococcus aureus and bacterial corneal ulcer model was established successfully. At 1d after inoculation,48 eyes were given levofloxacin eye drops when corneal ulcer was confirmed. Then slit lamp inspection and optical coherence tomography ( OCT) were performed to measure the central corneal ulcer depth. All the rabbits right eyes were treated with PTK, as an observation group,left eyes were not treated as a control group. The eye section were observed by slit lamp and central thickness of corneal ulcer was measured by OCT at 3 and 7d after this operation. Rabbits were sacrificed and the cornea was removed for pathological section 7d later. RESULTS: The corneal ulcers in both groups had a tendency to heal, showing a decrease in ulcer area and smoothness of the surface. There was no significant difference in the depth of corneal ulcer between the observation group and the control group before PTK (t=0.706,P=0.484). The difference between the two groups of eyes at 3 and 7d after PTK was obviously (P<0.05). CONCLUSION: PTK can effectively cure rabbit Staphylococcus aureus corneal ulcer and promote ulcer wound healing,which may be used for clinical treatment of patients with bacterial corneal lesions.

Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts.

To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation.

Establishment and application of median serum markers for second trimester screening in Qingdao region / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish the median of serum markers for second trimester screening in Qingdao region and to assess the influence of median correction on the performance of screening.</p><p><b>METHODS</b>Maternal serum alpha-fetoproteins (AFP), human chorionic gonadotrophin, free beta subunit (β -HCG) and unconjugated oestriol (uE3) were assayed for prenatal screening of 18 188 singleton pregnancies at 15-20(+ 6) weeks gestation from January 2009 to July 2010. The median of serum markers was calculated based on above results and applied for risk estimation in screening for fetal aneuploidy from August 2010 to March 2011. The screening performance, specified in terms of detection rates (DRs), false positive rates (FPRs) and odds of being affected given a positive result (OAPR) were compared between the two groups. The risks of 45 affected pregnancies detected during the study were estimated with both Caucasian and corrected medians.</p><p><b>RESULTS</b>The average level of AFP in local pregnancies was similar to that of the Caucasian population, whilst β -HCG and uE3 were respectively 11% and 33% higher than those of Caucasians. The multiple of median (MoM) value was between 0.94 and 1.02 for the dataset based on the corrected median. At a cut-off of l in 270, FPR has decreased from 5.2% to 4.9%, and DR of Down syndrome has increased from 60% to 69.2%, and OAPR has increased from 1:79 to 1:59 when evaluating risk based on the corrected median. For the 45 affected pregnancies, three Down syndrome pregnancies could be missed because their risk estimates were lower than the cut-off level based on Caucasian median.</p><p><b>CONCLUSION</b>It is useful to establish and apply population and laboratory-specific medians in order to improve the performance of prenatal screening and diagnosis.</p>

Evaluation of Down's syndrome screening methods using maternal serum biochemistry in the second trimester pregnancy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To provide basis for selecting the suitable method of Down's syndrome biochemical screening in the second trimester pregnancy.</p><p><b>METHODS</b>A total of 30 547 singleton pregnancies between 14 and 20(+ 6) weeks of pregnancy were collected and analyzed for maternal serum alpha-fetoproteins (AFP) and human chorionic gonadotrophin, free beta subunit (beta-HCG) with or without unconjugated estriol (uE3). The screening risks were calculated using the software Lifecycle. The detection rates and the cost of per Down's syndrome detected were calculated and compared. And four different methods were compared in a series of 64 serum samples from Down's syndrome pregnancies.</p><p><b>RESULTS</b>(1) Among the 64 affected cases, the detection rate of Down's syndrome was improved no matter in the double test (DT) or in the triple test (TT) if software Lifecycle (LC) was used to evaluate risks. And it was not suitable to evaluate risks with software 2T-Risks in the triple tests. (2) In the cohort of 30 547 singleton pregnancies, the detection rate of Down's syndrome with project DT-LC, which was double test using AFP and free beta-HCG together with software Lifecycle, and project TT-LC, which was triple test using AFP, free beta-HCG and uE3 together with software Lifecycle, was 56.25% and 57.14%, respectively. The former project was better because it decreased the false positive rate at a lower running cost.</p><p><b>CONCLUSION</b>The DT-LC is an effective screening strategy for second trimester detection of fetal Down's syndrome in mainland China.</p>