The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update

Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of multiple genetic and epigenetic alterations, which further lead to the activation of critical oncogenes or inactivation of tumor suppressor genes. HCC is characterized with multiple cancer hallmarks including their ability to proliferate, anti-apoptosis, invade, metastasis, as well as the emerging features such as stem cell properties and energy metabolic switch. The irreversible alterations at genetic level could be detected as early as in the pre-neoplastic stages and accumulate during cancer progression. Thus, they might account for the cancer initiating steps and further malignant transformation. In addition to genetic alterations, epigenetic alterations can affect the cancer transcriptome more extensively. Alterations in DNA methylation, histone modification, miRNAs, RNA editing, and lncRNAs might result in disrupted gene regulation networks and substantially contribute to HCC progression. In this review, the genetic and epigenetic alterations which significantly contribute to the malignant capabilities of HCC will be updated and summarized in detail. Further characterization of those critical molecular events might better elucidate the pathogenesis of HCC and provide novel therapeutic targets for treatment of this deadly disease.

Tumor suppressor genes on frequently deleted chromosome 3p in nasopharyngeal carcinoma / 癌症

Nasopharyngeal carcinoma (NPC) is among the most common malignancies in southern China. Deletion of genomic DNA, which occurs during the complex pathogenesis process for NPC, represents a pivotal mechanism in the inactivation of tumor suppressor genes (TSGs). In many circumstances, loss of TSGs can be detected as diagnostic and prognostic markers in cancer. The short arm of chromosome 3 (3p) is a frequently deleted chromosomal region in NPC, with 3p21.1-21.2 and 3p25.2-26.1 being the most frequently deleted minimal regions. In recent years, our research group and others have focused on the identification and characterization of novel target TSGs at 3p, such as RASSF1A, BLU, RBMS3, and CHL1, in the development and progression of NPC. In this review, we summarize recent findings of TSGs at 3p and discuss some of these genes in detail. A better understanding of TSGs at 3p will significantly improve our understanding of NPC pathogenesis, diagnosis, and treatment.

Comparative genomic hybridization: the profile of chromosomal imbalances in esophageal squamous cell carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To characterize the profile of chromosomal imbalances of esophageal squamous cell carcinoma (SCC) in Linzhou, the high prevalence area of Henan province.</p><p><b>METHODS</b>Comparative genomic hybridization (CGH) was used to examine 52 cases of primary SCC of esophagus.</p><p><b>RESULTS</b>Gains in part or in whole of chromosome 3q, 8q, 5p, 1q, 6q, 18p, 20q and losses of 3p, 1p, 9q, 19p, 4p, 8p were detected frequently in SCC (> 20%). Gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q were all significantly correlated with pathologic staging (P < 0.05). Gains of 8q, loss of 4p were linked to nodal metastasis (P < 0.05). Gains of 2p and loss of 4pq, 11q14-qter were associated with distant organ metastasis (P < 0.05).</p><p><b>CONCLUSION</b>These observations suggest that 3q, 8q, 5p, 1q, 6q, 18p, and 20q may contain SCC-related oncogenes; 3p, 1p, 9q, 19p, 4p and 8p may contain SCC-related tumor suppressor genes. It is likely that gain of 3q, 5p, 1q, 11q13-14 and loss of 4pq, 13q are the genetic aberrations critical for the development of esophageal carcinoma, whereas gains of 8q, 2p and loss of 4pq, 11q14-qter are considered later events associated with tumor progression and are thought to confer metastatic potential to esophageal carcinoma. Furthermore, nodal and distant organ metastases involve different genes.</p>

Molecular cytogenetic analysis for a familial complex chromosomal rearrangement / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine a complex chromosomal rearrangement by advanced molecular cytogenetic techniques and analyze its clinical effect.</p><p><b>METHODS</b>A complex chromosomal rearrangement (CCR) involved in chromosomes 5, 16 and 20 in a 29-year-old male carrier was determined by chromosomal microdissection and multicolor fluorescence in situ hybridization (M-FISH), and family degree investigation was further performed.</p><p><b>RESULTS</b>The karyotype of the case was a complex chromosomal translocation among chromosomes 5, 20 and 16, and accompanied with a band of chromosome 20 inserted into chromosome 5. His mother and sister both had the same abnormal karyotype by familial investigation.</p><p><b>CONCLUSION</b>The combined use of M-FISH and chromosome microdissection is a powerful tool to determine CCR. The complex chromosomal rearrangement could be transmitted stably in the family, but still the carriers could give birth to a healthy baby by chance.</p>

Expressions of E-cadherin in non-small cell lung cancer and it correlation with prognosis / 中华外科杂志

<p><b>OBJECTIVE</b>This study was to clarify E-cadherin expressions in non-small cell lung cancer (NSCLC) and its correlation with patients' prognosis.</p><p><b>METHODS</b>Tissue microarrays (TMAs) containing specimens from 365 different NSCLC were constructed, covering all stages and almost all histological types of this disease. Slides were immunohistochemically stained with antibodies against E-cadherin. Expression pattern of the protein was analyzed with relation to the clinicopathological. Correlations of the results with patients' overall survival were also examined.</p><p><b>RESULTS</b>Immunohistochemical staining revealed that E-cadherin protein was localized mainly on membranes and the cytoplasm of NSCLC tumors cells. Reduced E-cadherin expression was evident in 32.1%. Reduced E-cadherin expression significantly correlated with lymph nodes metastasis (chi(2) = 16.430, P = 0.001), histological dedifferentiation (chi(2) = 9.243, P = 0.010) and advanced clinical stage (chi(2) = 9.421, P = 0.024). There was no significant difference in E-cadherin expression between squamous cell carcinoma and adenocarcinoma. E-cadherin reduced expression correlated with a poor prognosis (P < 0.0001) in univariate analysis. Multivariate analysis showed a significantly lower survival probability for patients with reduced E-cadherin (P < 0.001), and E-cadherin was an independent prognostic factor for survival of NSCLC patients.</p><p><b>CONCLUSIONS</b>It suggests that dysfunction of E-cadherin has an important impact in the progression of lung cancer. As an independent prognostic factor, expression of E-cadherin can predict outcome of different group, together with conventional prognostic factors, and subsequently make appropriate management.</p>

Comparative genomic hybridization of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma in high-incidence region of esophageal carcinoma, Linzhou Henan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To characterize the profiles of chromosome imbalance in esophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA) from the high incidence area in Henan.</p><p><b>METHODS</b>Chromosomal aberrations of 37 samples of SCC and 30 GCA were analyzed by comparative genomic hybridization comparative genomic hybridization (CGH).</p><p><b>RESULTS</b>It was found that the most frequently detected gains were on chromosome arm 8q (78%), and followed by 3q, 5p, 6q and 7p. The most frequent loss was found on 3p (57%), and followed by 8p, 9q and 11q in SCC. For GCA, the most frequent gain was found on chromosome arm 20q (43%), and followed by 6q, 8q and 6p. The most frequent loss was on the chromosome 17p (57%), and followed by 19p, 1p and 4p.</p><p><b>CONCLUSION</b>The present findings demonstrate that gains of 8q, 3q and 5p, and losses of 3p, 8p, and 9q are characteristic profile of chromosome imbalance in SCC, and the gains of 20q, 6q and losses of 17p, 19p and 1p are characteristic profile of chromosome imbalance in GCA, which provide important theoretic information for identifying and cloning novel SCC/GCA-related genes.</p>