Research advances of chromosomal 8q24 aberrance in breast cancer / 中国肿瘤临床

With the development and application of microarray and high-throughput sequencing technology, it is possible to genomi-cally scan breast cancer associated CNV and SNPs. Multiple researches showed that the frequent aberrance of 8q24 was associated with breast cancer. Oncogenes such as MYC, PSCA and breast cancer associated loci are located in 8q24, and frequent amplification of 8q24 was proposed to be related with breast cancer development and prognosis. This review summarizes the association of the 8q24 amplification and SNPs with breast cancer by correlated genes on this locus.

Langer-Giedion Syndrome with 8q23.1–q24.13 Deletion by Complex Three-way Translocation

Langer-Giedion syndrome is a very rare genetic disorder that is caused by the deletion on chromosome 8q24.1, encompassing the TRPS1 and EXT1 genes. We describe a 5-month-old female patient who was admitted to our hospital with clinodactyly and weakness in both thumbs. The patient's karyotype was 46,XX,der(4)t(4;19)(q27;q11),der(8)t(4;8)(q27;q22.3),der(19)t(8;19)(q22.3;q11)del(8)(q23q24.1). Multiplex ligation-dependent probe amplification (MLPA) analysis showed that the patient had a heterozygous deletion, rsa 8q24(P064)x1 and rsa 8q24(P245)x1. Array comparative genomic hybridization (CGH) analysis further revealed three interstitial deletions spanning a total of 13.7 Mb at 8q23.1–q24.13. Based on clinical findings and confirmation by cytogenetic, MLPA, and array CGH analyses, the patient was diagnosed with sporadic Langer-Giedion syndrome with three-way translocations. This is the first case of Langer-Giedion syndrome with complex chromosomal rearrangements in Korea.

Relationship between single nucleotide polymorphisms in 2q35 rs13387042 and 8q24 rs13281615 and breast cancer risk of Han premenopausal women in Northern China / 中国癌症杂志

Background and purpose:Breast cancer as one of the most common malignant tumor among women in China, it accounts for 12.2% of all newly diagnosed breast cancers and 9.6% of all deaths from breast cancer worldwide. The aim of this study was to investigate the relationship between single nucleotide polymorphisms(SNPs) in 2q35rs13387042and 8q24 rs13281615and the risk of breast cancer in Han premenopausal women of Northern China. Methods:280 patients with breast cancer and 287 healthy controls in premenopausal state were genotyped for SNP 2q35rs13387042and 8q24 rs13281615 by the SNaPshot method, and compared the different genotypes and alleles with relation to breast cancer risk.Results:Differences of 2q35 rs13387042 genotype frequencies between breast cancer and control were signiifcantly different (P=0.017). No statistically signiifcant difference of 8q24 rs13281615 genotype frequencies between breast cancers and controls was found (P=0.967). The results of logistic regression showed that the carriers of GA genotype and GA+ AA genotype increased risk for breast cancer compared to the carriers with 2q35 rs13387042 GG genotype(OR=1.793, 95%CI: 1.177-2.733,P=0.007;OR=1.691, 95%CI: 1.122-2.550,P=0.012), but not the carriers of AA genotype; Compared with G allele, A allele signiifcantly increased the risk of breast cancer(OR= 1.505, 95%CI: 1.033-2.193,P=0.033). The carriers of AG genotype or GG genotype or AG+GG genotype did not confer risk for breast cancer compared to the carriers with 8q24 rs13281615 AA genotype(OR=0.992, 95%CI: 0.660-1.490,P=0.968;OR=1.047, 95%CI: 0.642-1.708,P=0.853;OR=1.007, 95%CI: 0.682-1.487,P=0.971); Compared with A allele, G allele did not increase the risk of breast cancer(OR=1.021, 95%CI: 0.809-1.288,P=0.863).Conclusion:This experiment veriifed that 2q35 rs13387042 polymorphism site increased risk of breast cancer susceptibility among Han premenopausal women of Northern China. There was not any signiifcant association between 8q24 rs13281615 poly-morphism site and breast cancer susceptibility among Han premenopausal women of Northern China under the current sampling scale.

A correlation study between ITGA6 gene, chromosome 8q24, MSMB genes and prostate cancer / 中华泌尿外科杂志

Objective To explore the correlation between ITGA6 gene (rs12621278, G), MSMB gene (rs10993994, T), chromosome 8q24 (rs10086908, T) and prostate cancer (PCa) in Beijing residents, and to explore the correlation between genotype and phenotype in PCa patients. Methods PCa patient phenotypes were collected including clinical, genetic, dietary habits, hobbies and blood samples. ITGA6 gene (rs12621278, G), chromosome 8q24 (rs10086908, T) and MSMB gene (rs10993994, T) compared the allele distribution between 112 PCa and 91 healthy control age matched patients. The genotype and phenotype analysis was conducted in the 2 groups. Results Between the case and control groups, only rs10993994, T of MSMB gene (case 56.4%,control 46.2%) was significantly different (P=0.001; OR=1.97, 95%CI:1.28-3.04). The rs10086908, T of 8q24 (case 83.5%, control 79.2%) and rs12621278, G of ITGA6 gene (case 27.2%, control 27.0%) were not significantly associated with PCa in the study sample (P>0.05). Quantitative trait analysis showed that the disease duration of ITGA6 risk genotypes (G/G,1.40±0.55 years) in PCa patients was significantly shorter (P=0.003) than the other genotype carriers (A/G, 4.38±3.10 years; A/A, 2.37±1.84 years). Conclusion The genetic variation in MSMB is possibly associated with PCa susceptibility, suggesting that MSMB genes might be associated with PCa in a Chinese population.

High Frequency of Genetic Alterations in Non-small Cell Lung Cancer Detected by Multi-target Fluorescence In Situ Hybridization

Detection of genetic alterations could provide a tool as an adjuvant for the diagnosis of non-small cell lung cancer (NSCLC) and to define patients at risk for early relapse. In this study, a multi-target fluorescence in situ hybridization (FISH) assay was conducted to investigate the correlation between the alterations of chromosomes, including 5p15.2, 6p11.1-q11, 7p12, and 8q24.12-q24.13 (LaVysion Test), and clinicopathological variables, and to clarify the potential of the multi-target FISH assay in 37 NSCLC. The most notable finding was the higher frequency of a gain in chromosome 5p15.2 in early-stage (I+IIa) lung cancers. The frequency of the gain was 81.3% (16/22) in stage I tumors. The frequencies of gains in 6p11.1-q11 and 8q24.12-q24.13 were 61.5% (8/13) and 84.6% (11/13) in stage IIIa cancers, as compared with lower frequencies in stage I tumors at 25.0% and 31.3%, respectively. There was also a significant difference in the histological type. Our results suggest that a gain in 6p11.1-q11 and 8q24.12-q24.13 plays an important role in tumor progression and is associated with histological differentiation. On the other hand, gene amplification in the 5p region was one of the most consistent alterations in early-stage lung cancer, and thus a series of genes in the critical 5p15.2 region might potentially associated with the development of lung cancer.