Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression. @*Materials and Methods@#AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3’s correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3’s impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected. @*Results@#AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines. @*Conclusion@#AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.

Result of carrier screening for spinal muscular atrophy among 3049 reproductive-age individuals from Yunnan region / 中华医学遗传学杂志

OBJECTIVE@#To perform carrier screening for spinal muscular atrophy (SMA) among 3049 reproductive-age individuals from Yunnan region and determine the copy number of survival motor neuron (SMN) gene and carrier frequencies.@*METHODS@#Multiplex ligation-dependent probe amplification (MLPA) was used to determine the copy number of exon 7 of SMN1 and SMN2 genes and identify those with a single copy of SMN1 gene. Prenatal diagnosis was performed for couples whom were both found to be SMA carriers.@*RESULTS@#In total 62 SMA carriers were identified among the 3049 subjects, which yielded a carrier frequency of 1 in 49 (2.03%). No statistical difference was found in the carrier frequency between males and females (1.91% vs. 2.30%, P>0.05). Respectively, 1.3% (41/3049) and 0.69% (21/3049) of the carriers were caused by heterozygous deletion and conversion of the SMN1 gene. The average copy number for SMN1 alleles was 1.99. Two couples were found to be both as SMA carriers, for whom the birth of an affected fetus was avoided by prenatal diagnosis.@*CONCLUSION@#No difference was found in the carrier frequency of SMA-related mutations between the two genders in Yunnan region, which was in keeping to an autosomal recessive inheritance pattern. Determination of the carrier frequency for SMA and SMN gene variants may provide a basis for genetic counseling and prenatal diagnosis for the disease.

Application of BoBs technique for detecting common chromosome microdeletion and microduplication syndromes / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish a strategy for screening and diagnosing common microdeletion and microduplication syndromes among children with idiopathic mental retardation and development abnormalities.</p><p><b>METHODS</b>Potential chromosomal variations among patients with unexplained mental retardation, cardiac anomalies, particular facial features, learning disabilities and other clinical characteristics were detected with bacterial artificial chromosome BACs-on-Beads (BoBs) technique and karyotyping. Positive results were verified with array-based comparative genomic hybridization (Array-CGH).</p><p><b>RESULTS</b>Fifty eight of the 60 patients had a normal chromosome karyotype. Ten patients with microdeletion and microduplication syndromes were detected by BoBs, which included two positive cases identified through chromosome karyotyping. Two patients were respectively diagnosed as Smith-Magenis syndrome and Prader-Willi/Angelman syndrome by BoBs and the results were confirmed by Array-CGH.</p><p><b>CONCLUSION</b>BoBs is capable of detecting chromosome microdeletion and microduplication with high specificity and throughput, which can compensate the shortcomings of conventional cytogenetic technology and will be widely applied for clinical diagnosis.</p>

Prenatal diagnosis of chromosome abnormalities and nine microdeletion syndromes using both traditional karyotyping and BoBs / 中华妇产科杂志

Objective To evaluate a new prenatal diagnosis model of chromosomal abnormalities and nine microdeletion syndromes by using both traditional karyotyping and a newly-developed rapid prenatal diagnosis technology, BACs-on-Beads (BoBs) technique. Methods From June 2012 to December 2014, 807 pregnant women with high risk after screening or with other indicators, were performed amniocentesis. Traditional karyotyping and BoBs were employed simultaneously for prenatal diagnosis. Results Thirty-two cases with chromosome aneupoidies were successfully detected both by BoBs and karyotyping, including 18 cases of trisomy 21, 6 cases of trisomy 18, 1 case of trisomy 13, and 7 cases with sex chromosome abnormality. All 8 fetuses with chromosome structural abnormalities detected by karyotyping were missed by BoBs;while BoBs contributed more in detection of five microdeletion syndrome cases, including 3 cases of DiGeorge syndromes (two with microduplication and one with microdeletion), one case of Miller-Dieker syndrome, and one case of Wolf-Hirschhorn syndrome. Conclusion Combined use of traditional karyotyping and BoBs, is a rapid and effective prenatal diagnosis model that may enlarge our horizon on chromosomal diseases and should be widely used in future clinical service.

Study on key techniques and intervention in reducing birth defects / 中华妇产科杂志

ObjectiveTo investigate key techniques and intervention in reducing birth defects. Method Down's syndrome (DS), trisomy-18 (Edwards syndrome, ES), neural tube defects (NTD), Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA), thalassemia, and glucose-6-phosphate dehydrogenase deficiency (G6PD) were chosen as target disease. From Jan. 2007 to Dec. 2009, the condition of intake folie acid were investigated in 5004 pregnant women in Panlong District and Wuhua District of Kunming City. All of the 27 660 pregnant women undergoing prenatal examination were enrolled into the study from the First People's Hospital of Yunnan Province, the Second People's Hospital of Yunnan Province, the First People's Hospital of Qujing City, the Second People's of Qujing City, Qujing Women and Children's Hospital, People's Hospital of Lincang City, Kunming Maria Women's Hospital, Maternal and Infant's Care Unit of Panlong District of Kunming City, Maternal and Infant's Hospital of Dali City. The screening was performed on serum of those pregnant women at 8 -20 +6 gestational weeks. Prenatal cytogenetic analysis and fetal ultrasonogrspy were performed on the high risk or indicated women after genetic counseling. DNA analysis was administered on those women with family or childbearing history of DMD,SMA,thalassemia,orG6PD. Outcomeof pregnancywasfolloweduptoevaluatetheeffectof intervention. ResultsApproximately 30. 10％ (1506/5004) of pregnant women were administered by oral folic acid during perinatal period. Two thousand three hundred and thirteen women with high risks of DS,ES, or NTD fetuses were observed among 27 660 undergoing maternal serum screening. Two thousand and ninety-six pregnant women including two twins pregnant women were performed cytogenetic analysis. Other 67 pregnant women at high risk of DMD, SMA, thalassemia, and G6PD accepted genetic counseling and prenatal gene analysis. Two thousand one hundred and sixty-three pregnant women (2165 fetuses) underwent prenatal examination. One hundred and two cases chromosome abnormalities, 17 cases NTD, 4 cases DMD, 1 cases α-thalassemia major were found. All of the 91 fetuses with major birth defects were terminated after genetic counseling. Another affected DS fetus in a twin pregnancy dead intrauterine at 24 gestational weeks. Thirty-two women bearing fetuseswithbalancedtranslocations orinversionscontinuedtheir pregnancies. Totally 2071 normal term fetuses were born in the prenatal diagnosis group. Two fetuses with normal chromosome were lost within 1 week after amniocentesis. Four affected DS fetuses were born from their high risk mothers who refused further prenatal diagnosis service. In a random sampling follow-up cohort of 5000 mothers at low risk, none of affected child suffering target diseases was found. The DS detection rate of maternal serum screening was 84％ (27/32), with the false positive rate was 6. 153％ (1702/27 660).ConclusionsFolic acid intake before conception and in the first trimester would reduce the risk of birth defects, only 1/3 reproductive women took folie acid actively. Maternal serum screening could effectively detect high risk of DS, ES and NTD. The genetic counseling is critical in women at high risk or who had family history of inherited disorders. The prenatal screening and diagnosis combined with routine obstetric care could reduce the incidence of major birth defects, which should become prenatal care strategy in our country.