Prognostic values of chromosome 18q microsatellite alterations in stage Ⅱ colonic carcinoma

AIM: To investigate the prognostic value of chromosome 18q microsatellite alterations (MA) in stage Ⅱ colon cancer. METHODS: One hundred and six patients with sporadic stage Ⅱ colon cancer were enrolled in this study. DNA was extracted from formalin-fixed, paraffin-embedded tumor and adjacent normal mucosal tissue samples. MA, including loss of heterozygosity (LOH) and microsatellite instability (MSI), was analyzed by polymerase chain reaction, polyacrylamide gel-electrophoresis and DNA sequencing at 5 microsatellite loci on chromosome 18q (D18S474, D18S55, D18S58, D18S61 and D18S64).RESULTS: Among the 102 patients eligible for MA information, the overall frequencies of LOH, high and low frequency MSI/microsatellite stable were 49.0%, 17.6% and 82.4%, respectively. The high frequency of 18q-LOH was signif icantly associated with the poor 5-year overall survival (OS) (P=0.008) and disease free survival (P=0.006). High levels of MSI were significantly associated with a longer 5-year OS (P=0.045) while the higher frequency of 18q-LOH at the loci of D18S474 and D18S61 was significantly associated with a poorer 5-year OS (P=0.010 and 0.005, respectively). But multivariate analysis showed that only the frequency of 18q-LOH was significantly associated with the prognosis of the disease. CONCLUSION: High frequency of 18q-LOH is an independent prognostic factor indicating poor prognosis of the patients with stage Ⅱ colon cancer.

Evidence of increased chromosomal instability in infertile males after exposure to mitomycin C and caffeine

Aim： To evaluate the genetic instability of 11 fertile and 25 infertile men. Methods： The methodology of sister chromatid exchanges （SCEs） was applied to cultures of peripheral blood lymphocytes, and the levels of SCEss were analyzed as a quantitative index of genotoxicity, along with the values of the mitotic index （MI） and the proliferation rate index （PRI） as qualitative indices of cytotoxicity and cytostaticity, respectively. The genotoxic and antineoplastic agent, mitomycin C （MMC）, and caffeine （CAF） - both well-known inhibitors of DNA repair mechanism - were used in an attempt to induce chromosomal instability in infertile men, so as to more easily detect the probable underlying damage on DNA. Results： Our experiments illustrated that infertile men, compared with fertile ones, demonstrated a statistically significant DNA instability in peripheral blood lymphocytes after being exposed simultaneously to MMC and CAF. Conclusion： The current study showed vividly that there was genetic instability in infertile men which probably contributes to the development of an impaired reproductive capacity. （Asian JAndro12006 Mar; 8： 199-204）

FREQUENT ALLELIC IMBALANCE AND CYTOGENETIC DELETION ON THE SHORT ARM OF CHROMOSOME 1 IN NASOPHARYNGEAL CARCINOMA

Objective: To construct a fine map of the loss of chromosome lpter-p36.11 region in nasopharyngeal carcinoma (NPC) using PCR-LOH technique. Methods: DNA extracted from separated cancerous cells and their mated noncancerous lymphocytes from 47 cases of NPC biopsies were analyzed by means of PCR-LOH to detect 20 loci spanning chromosome lpter-p36.11 region in NPC. Results: In 47 NPC cases, 37 (82.2%) cases showed at least one loci LOH. The highest frequency of less of heterozygosity (LOH) at all 20 loci was found at loci DIS234 (50. 0%) on lp36.13 and loci DlS2644 (37.5%) on lp36.22. There was a statistically significant difference between DlS234 LOH frequency (60%, 9/15) in early stage and that (50. 0%, 8/16) in advanced stage (P>0.05). Of all 20 STSs (sequence tqgged-site, STS), DIS243 (37.5%) and DIS199 (30.2%) showed the highest frequency of MI (microsatellite instability) on lp36.33 and lp36.21, respectively. In addition, several cases showed a contiguous stretch of allelic loss in a different level. Conclusion: Two minimal deletion regions (MDR) on the short arm of chromosome 1 were seated at lp36.13 (DIS234, 2.0 cm) and lp36.22 (DIS436-DIS2644, 6.3 cm) respectively, indicating that one or more candidate tumor suppressor gene (TSG) in the two regions may be involved in NPC pathogenesis in an early clinical stage.

Metabolomic alterations and chromosomal instability status in gastric cancer

AIM To explore the correlation of metabolomics profiles ofgastric cancer(GC) with its chromosomal instability(CIN) status.METHODS Nineteen GC patients were classified as CIN and nonCIN type by The Cancer Genome Atlas Research Group system, based on 409 oncogenes and tumor suppressor genes sequenced. The aqueous metabolites of the GC tumor and its surrounding adjacent healthy tissues were identified through liquid chromatographymass spectrometry. Groups were compared by defining variable importance in projection score of > 1.2, a fold change value or its reciprocal of > 1.2, and a P value of < 0.05 as a significant difference.RESULTS In total,twelve men and seven women were enrolled, with a median age of 66 years(range, 47-87 years). The numbers of gene alterations in the CIN GC group were significantly higher than those in the non-CIN GC(32-218 vs 2-17; P < 0.0005). Compared with the adjacent healthy tissues, GC tumors demonstrated significantly higher aspartic acid, citicoline, glutamic acid, oxidized glutathione, succinyladenosine, and uridine diphosphate-Nacetylglucosamine levels, but significantly lower butyrylcarnitine, glutathione hydroxyhexanoycarnitine, inosinic acid, isovalerylcarnitine, and threonine levels(all P < 0.05). CIN tumors contained significantly higher phosphocholine and uridine 5'-monophosphate levels but significantly lower beta-citryl-L-glutamic acid levels than did non-CIN tumors(all P < 0.05). CIN GC tumors demonstrated additional altered pathways involving alanine, aspartate, and glutamate metabolism, glyoxylate and dicarboxylate metabolism, histidine metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis.CONCLUSION Metabolomic profiles of GC tumors and the adjacent healthy tissue are distinct, and the CIN status is associated with downstream metabolic alterations in GC.

Role of chromosomal instability and clonal heterogeneity in the therapy response of breast cancer cell lines

Objective:Chromosomal instability(CIN)is a hallmark of cancer characterized by cell-to-cell variability in the number or structure of chromosomes,frequently observed in cancer cell populations and is associated with poor prognosis,metastasis,and therapeutic resistance.Breast cancer(BC)is characterized by unstable karyotypes and recent reports have indicated that CIN may influence the response of BC to chemotherapy regimens.However,paradoxical associations between extreme CIN and improved outcome have been observed.Methods:This study aimed to 1)evaluate CIN levels and clonal heterogeneity(CH)in MCF7,ZR-751,MDA-MB468,BT474,and KPL4 BC cells treated with low doses of tamoxifen(TAM),docetaxel(DOC),doxorubicin(DOX),Herceptin(HT),and combined treatments(TAM/DOC,TAM/DOX,TAM/HT,HT/DOC,and HT/DOX)by using fluorescence in situ hybridization(FISH),and 2)examine the association with response to treatments by comparing FISH results with cell proliferation.Results:Intermediate CIN was linked to drug sensitivity according to three characteristics:estrogen receptorα(ERα)and HER2 status,pre-existing CIN level in cancer cells,and the CIN induced by the treatments.ERα+/HER2-cells with intermediate CIN were sensitive to treatment with taxanes(DOC)and anthracyclines(DOX),while ERα-/HER2-,ERα+/HER2+,and ERα-/HER2+cells with intermediate CIN were resistant to these treatments.Conclusions:A greater understanding of CIN and CH in BC could assist in the optimization of existing therapeutic regimens and/or in supporting new strategies to improve cancer outcomes.

Glycerophospholipids pathways and chromosomal instability in gastric cancer: Global lipidomics analysis

BACKGROUND Based on the breakthrough of genomics analysis, The Cancer Genome Atlas Research Group recently proposed an integrative genomic analysis, dividing gastric cancer(GC) into four subtypes, characterized by the chromosomal instability(CIN) status. However, the CIN status of GC is still vaguely characterized and lacking the valuable easy-to-use CIN markers to diagnosis in molecular and histological detection.AIM To explore the associations of CIN with downstream lipidomics profiles.METHODS We collected cancerous and noncancerous tissue samples from 18 patients with GC; the samples were divided into CIN and non-CIN types based on the system of The Cancer Genome Atlas Research Group and 409 sequenced oncogenes and tumor suppressor genes. We identified the lipidomics profiles of the GC samples and samples of their adjacent noncancerous tissues by using liquid chromatography–mass spectrometry. Furthermore, we selected leading metabolites based on variable importance in projection scores of > 1.0 and P <0.05.RESULTS Twelve men and six women participated in this study; the participants had a median age of 67.5 years(range, 52–87 years) and were divided into CIN(n = 9)and non-CIN(n = 9) groups. The GC samples exhibited distinct profiles of lysophosphocholine, phosphocholine, phosphatidylethanolamine,phosphatidylinositol, phosphoserine, sphingomyelin, ceramide, and triglycerides compared with their adjacent noncancerous tissues. The glycerophospholipid levels(phosphocholine, phosphatidylethanolamine, and phosphatidylinositol)were 1.4-to 2.3-times higher in the CIN group compared with the non-CIN group(P < 0.05). Alterations in the glycerolipid and glycerophospholipid pathways indicated progression of GC toward CIN.CONCLUSION The lipidomics profiles of GC samples were distinct from those of their adjacent noncancerous tissues. CIN status of GC is primarily associated with downstream lipidomics in the glycerophospholipid pathway.

Molecular Profile of Human Serine Palmitoyltransferase-1 Proximate of Chromosome 9 Disease Susceptibility Gene Cluster in Inflammatory Cancer Cell Lines

Background: Over 1100 genes have been annotated for human chromosome 9, including disease genes implicated in inflammation, atherosclerosis, cancer and neurodegeneration. The serine palmitoyltransferase-1, SPTLC1, gene is at the 9q22.2 cytogenetic band, a high G+C content region with common genetic alterations sufficient to modify cellular behavior. The sequence is highly conserved among diverse species from bacteria to humans, including a recently discovered 126 nucleotide alternate open reading frame, AltORF. The protein encoded by the reading frames has domains of biological interest and considerable overlapping molecular functions associated with cellular behavior and cancer progression. Methods: Here we examined molecular features of SPTLC1 in a group of inflammation associated cancer cell lines SKN-SH, MDA-PCa, Glioma LN18, PC3 and 647V. Subcellular localization of SPTLC1 was assessed by immunofluorescence microscopy and recombinant green fluorescent protein expression. In addition, PCR, DNA sequencing and bioinformatics analysis were used for molecular profiling of the SPTLC1 genomic and reverse transcribed cDNA fragments. Results: SPTLC1 is detected in all cell lines examined, with intense peri-nuclear staining, consistent with localization in the cytoplasm. Genomic DNA sample, but not the cD NA of SKN cells could be amplified with an AltORF primer set. The PC3 and MDA-PCa cancer cell lines which are both of prostate origin, show differences in SPTLC1 PCR amplification. Similar levels of SPTLC1 AltORF transcripts were detected by quantitative RT-PCR in all cell lines, except the PC3 cell line with low transcript level whose cDNA did not generate nucleotide base sequence information. Conclusions: This is the first reported transcriptional expression of the SPTLC1 AltORF for the inflammation associated human cancer cell lines. Interestingly, it is proximate of oncogenic cancer susceptibility genes and distal of tumor suppressor genes, the high content of short nucleotide repeats in the SPTLC1 AltORF sequence suggesting the region may be genetically unstable. This nominal functional genomics report on the human SPTLC1 AltORF will contribute to compiling a more detailed SPTLC1 gene ontology and is expected to help shed more insight into unique molecular attributes of SPTLC1 in the context of cancer cell behavior, malignant progression and the design of treatment for inflammation associated cancers.

微核激活cGAS-STING信号通路的机制及其肿瘤免疫功能

环鸟苷酸-腺苷酸合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路可监测微生物入侵和组织损伤等生理病理异常状态,是天然免疫系统的重要组成之一。作为DNA感受器,cGAS主要识别异常定位于细胞质的双链DNA(dsDNA),通过催化合成二级信使环鸟苷酸-腺苷酸启动由STING介导的Ⅰ型干扰素和炎症信号通路。微核是有丝分裂后期染色体错误分离的产物,也是细胞质dsDNA的重要来源之一。作为一类不稳定的亚细胞器结构,微核核膜倾向于不可逆的破裂,导致微核基因组DNA暴露在细胞质中。暴露的微核基因组DNA招募并激活cGAS-STING信号通路,诱导STING下游信号通路活化,包括Ⅰ型干扰素信号通路和经典核因子κB(NF-κB)信号通路,导致细胞衰老、细胞凋亡和细胞自噬的发生,从而介导免疫系统的活化以清除肿瘤细胞,或者直接诱导肿瘤细胞死亡。另外,STING持续激活诱导的内质网应激,以及慢性Ⅰ型干扰素信号通路和非经典NF-κB信号通路的活化,营造了免疫抑制的肿瘤微环境,导致肿瘤细胞免疫逃逸,促进肿瘤转移和肿瘤细胞存活。因此,在肿瘤的发生发展和治疗过程中,活化的cGAS-STING免疫通路扮演着抑制或促进肿瘤的双重作用。本文阐述了肿瘤微环境中微核诱导cGAS-STING免疫通路活化的机制研究进展,探讨了其在肿瘤发生发展和治疗中的潜在重要作用。

DNA损伤反应缺陷与高风险神经母细胞瘤

神经母细胞瘤(neuroblastoma,NB)是儿童最常见的颅外实体肿瘤。其中高风险患者进展快、预后差。分子遗传学上,高风险NB特征性表现为染色体不稳定性,以DNA损伤反应(DNA damage response,DDR)缺陷为主。目前已有靶向DDR的抑制剂(如ATR、ATM、PARP、CHK1和WEE1抑制剂)用于高风险NB的治疗。应用DDR缺陷及靶向抑制剂等方式可为高风险NB的精准诊断及治疗提供参考,有望成为治疗高风险NB的新策略。

Genetic alterations in hepatocellular carcinoma: An update

Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC.

Microsatellite instability and MLH1 promoter hypermethylation in colorectal cancer

Colorectal cancer （CRC） is caused by a series of genetic or epigenetic changes, and in the last decade there has been an increased awareness that there are multiple forms of colorectal cancer that develop through different pathways. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and most of hereditary nonpolyposis cancers. Tumors with a high frequency of microsatellite instability tend to be diploid, to possess a mucinous histology, and to have a surrounding lymphoid reaction. They are more prevalent in the proximal colon and have a fast pass from polyp to cancer. Nevertheless, they are associated with longer survival than stage-matched tumors with microsateUite stability. Resistance of colorectal cancers with a high frequency of microsatellite instability to 5-fluorouracilbased chemotherapy is well established. Silencing the MLH1 gene expression by its promoter methylation stops the formation of MLH1 protein, and prevents the normal activation of the DNA repair gene. This is an important cause for genomic instability and cell proliferation to the point of colorectal cancer formation. Better knowledge of this process will have a huge impact on colorectal cancer management, prevention, treatment and prognosis.

Colorectal cancer carcinogenesis:a review of mechanisms

Colorectal cancer(CRC) is the second most common cancer in women and the third most common in men globally. CRC arises from one or a combination of chromosomal instability, Cp G island methylator phenotype, and microsatellite instability. Genetic instability is usually caused by aneuploidy and loss of heterozygosity. Mutations in the tumor suppressor or cell cycle genes may also lead to cellular transformation. Similarly, epigenetic and/or genetic alterations resulting in impaired cellular pathways, such as DNA repair mechanism, may lead to microsatellite instability and mutator phenotype. Non-coding RNAs, more importantly micro RNAs and long non-coding RNAs have also been implicated at various CRC stages. Understanding the specific mechanisms of tumorigenesis and the underlying genetic and epigenetic traits is critical in comprehending the disease phenotype. This paper reviews these mechanisms along with the roles of various non-coding RNAs in CRCs.

Prognostic significance of microsatellite alterations at 1p36 in cholangiocarcinoma

AIM： To investigate loss of heterozygosity （LOH） and microsatellite instability （MSI） on the chromosomal region 1p36-pter in cholangiocarcinoma （CCA） patients and determine the association between microsatellite alterations and clinicopathological parameters. METHODS： Ten polymorphic microsatellite markers were determined for LOH and MSI using GS-3000 gel scan fragment autoanalyzer. RESULTS： Sixty-eight out of 90 cases （75.6%） showed LOH in one or more loci. LOH was found most frequently at DIS199 （40.0%）, DIS507 （34.6%）, DIS2845 （30.5%）, and DIS2734 （30.1%）. MSI was found in 34 of 90 cases （37.8%） at one or more loci. Fine mapping at lp36 showed two distinctive regions of common loss, which were D1S2845 and the 25.5-cM region between D1S507 and D1S2734, indicating the existence of putative tumor suppressor genes that is likely to play important roles in the development of CCA. Patients with LOH at D1S234 showed less lymphatic invasion （P = 0.017）, whereas patients with LOH at D1S2676 exhibited more lymphatic invasion than those without （P = 0.031）. LOH at D1S2845 showed a significant correlation with nerve invasion （P = 0.029）. Moreover, patients who demonstrated MSI at D1S228 showed a poor prognosis （P = 0.0026）. CONCLUSION： Allelic loss plays a major role in microsatellite alterations at chromosome lp36, which may contribute to carcinogenesis and pathogenesis of liver fluke related CCA and these alterations can be used as molecular prognostic indicators for CCA patients.

Genomic Instability in Cancer II: 4N-Skewed (90°) Reductive Division via Fragile Sites to Fitness Increase for Solid and Hematological Cancer Beginnings

The objective herein was to connect the ontogeny process of diplochromosomal, amitotic, 4n-skewed division-system, to cytogenetic deficiency lesions in satellite, repetitive DNAs, especially in the chromosomal fragile sites, some 100 distributed over the genome. These latter studies had shown that chemical induced replication-stress led to un-replicated lesions in these fragile sites, which from inaccurate repair processes caused genomic instability. In the chain of events of the ontogeny process to the special tetraploidy, it was proposed that primary damaged human cells could undergo replication stress from repair-process present during cell replication, a suggestion verified by X-ray damaged cells producing the unstable fragile sites (see text). The cancer-importance for therapy is recognition of cell cycle change for the 4n derivative fitness-gained, diploid progeny cells. An open question is whether RB controlling G1 to S-period is mutated at this suggested tumorigenesis initiating phase, and if so, with what consequences for therapy. The fragile site studies further showed that repair of repetitive DNAs could produce two types of genomic changes: single gene mutations and CNVs, which were here shown to be chromosomally located on “borders” to repairing satellite lesions. This genomic placement was found to correspond to mutations identified in tumor sequencing (p53, Rb, MYC), favoring a bad luck location for their cancer “mutational nature”. The CNVs in cancers, are here seen as molecular expressions of long-known cytogenetic HSRs and DMs also with demonstrated origin from amplifications of single genes. Over-expression of oncogenes was hinted of being from duplications, but Drosophila genetics demonstrated the opposite, gene inactivation. The reduced eye-size from dominant, BAR-Ultra-Bar-eye phenotypes, was caused by duplications, inactivating the genetic system for eye-size. The finding of CNVs showing “evasion” of the immune system suggests, inactivation of immune-determining genetics. Since mutated genes on borders to satellite DNAs are a fact in hematological cancers, the 4n-skewed division-system is suggested to replace debated leukemogenesis with fitness-gain from molecular mutations. For these cancers the question is how normal bone marrow cells attain genomic damage for special tetraploidy, which was referred to studies of cells moving in artificial marrow-like substrate, needing serious attention.

Aberration of biotransportmative activity of macrosomal liver ferments and cytogenetic instability on the background of opisthorChiasis invasion in man and animals.

It was shown that the level of cells with chromo-some aberration was elevated in a patient withopisthorchiasis in addition to this the possibi-lity of canceraus hepatic transformation increasedsharply.The investigation of biotransformativeactivity of S-9,fraction of microsomes

CENPA表达与癌症的关系研究进展

异常的细胞分裂导致整个染色体不稳定是癌症发生的标志。染色体准确分离在细胞分裂中有着重要作用,而着丝粒则是染色体准确分离的关键。着丝粒蛋白A(CENPA)是一种着丝粒特异性组蛋白H3样变异基因,也是着丝粒蛋白家族中研究最广泛的因子,在多种癌症中过表达。CENPA过表达可能导致着丝粒异染色质沿染色体臂扩散,导致微管-动粒锚定缺陷,最终导致基因组不稳定。因此,探讨CENPA过表达与癌症进展的关系,对寻找新的靶向治疗方法有着重要意义。

Functions of spindle check-point and its relationship to chromosome instability

It is generally believed that the equal distribution of genetic materials to two daughter cells during mitosis is the key to cell health and development. During the dynamic process, spindle checkpoint plays a very important role in chromosome movements and final sister chromatid separation. The equal and precise segregation of chromosomes contributes to the genomic stability while aberrant separations result in chromosome instability that causes pathogenesis of certain diseases such as Down’s syndrome and cancers. Kinetochore and its regulatory proteins consist of the spindle checkpoint and determine the spatial and temporal orders of chromosome segregation.

多倍体肝细胞的生理功能及其病理性改变的相关疾病

成人肝脏中20%~50%的肝细胞为含2套以上染色体的多倍体细胞,是独特的多倍体器官。肝细胞多倍体化始于断奶时胰岛素信号的改变,受多种细胞周期调控因子控制,实现在多倍体细胞比例、倍性和空间分布等方面的调控,对肝脏代谢、再生和抑制肿瘤形成有重要作用。但在慢性病毒性肝炎和非酒精性脂肪肝病中,肝细胞可因细胞周期检查点抑制、氧化应激出现病理性多倍体化并参与疾病进程。区分多倍体肝细胞在生理和病理条件下的异同,有助于更好地认识慢性肝脏病与肿瘤发生的关系。

Centrosome aberrations and chromosome instability contribute to tumorigenesis and intratumor heterogeneity

Centrosomes serve as the major microtubule organizing centers in cells and thereby contribute to cell shape,polarity,and motility.Also,centrosomes ensure equal chromosome segregation during mitosis.Centrosome aberrations arise when the centrosome cycle is deregulated,or as a result of cytokinesis failure.A long-standing postulate is that centrosome aberrations are involved in the initiation and progression of cancer.However,this notion has been a subject of controversy because until recently the relationship has been correlative.Recently,it was shown that numerical or structural centrosome aberrations can initiate tumors in certain tissues in mice,as well as invasion.Particularly,we will focus on centrosome amplification and chromosome instability as drivers of intra-tumor heterogeneity and their consequences in cancer.We will also discuss briefly the controversies surrounding this theory to highlight the fact that the role of both centrosome amplification and chromosome instability in cancer is highly context-dependent.Further,we will discuss single-cell sequencing as a novel technique to understand intra-tumor heterogeneity and some therapeutic approaches to target chromosome instability.

鼻咽癌染色体16q22-24遗传不稳定性的研究

目的：研究鼻咽癌染色体１６ｑ２２－２４的遗传稳定性。方法：用染色体１６ｑ２２－２４上的８对微卫星多态性标记分析 ５０例鼻咽癌的杂合性缺失（ｌｏｓｓ ｏｆ ｈｅｔｅｒｏｚｙｇｏｓｉｔｙ， ＬＯＨ）与微卫星不稳定性 （ｍｉｃｒｏｓａｔｅｌｌｉｔｅ ｉｎｓｔａｂｉｌｉｔｙ， ＭＳＩ）。结果：至少一个位点发生ＬＯＨ的肿瘤占４８％（２４／５０），ＭＳＩ的发生率为１８％（９／５０）。但这些变化均散在分布，未见高频共同缺失区和微卫星不稳定区；其变化在早期（Ⅰ／Ⅱ期）和晚期（Ⅲ／Ⅳ期）病人之间有显著性差异（Ｐ＜０．０５）。结论：染色体１６ｑ２２－２４区的遗传不稳定性的变化可能与鼻咽癌的发病有关，该区是否存在鼻咽癌相关基因有待进一步探讨。