ABSTRACT
It has been noted for decades that cancer is essentially a genomic disease. Benefiting from the latest development of high-throughput sequencing and bioinformatics technologies, a variety of genetic alterations have been identified for their roles in cancer occurrence and development, giving rise to new opportunities for anti-cancer drug discovery. In particular, the rapid advancement of cancer genomics has paved the way for the precision medicine that has gained compelling achievement in the past years and significantly benefited cancer patients. In this review, we summarize the main types of genomic abnormalities in cancer, the application of functional genomics research in cancer research, and in particular the translational application of cancer genomics in clinical diagnosis, drug discovery and cancer precision medicine. With this review, we hope to better understand cancer genomics research and provide future perspectives for its application in precision medicine.
ABSTRACT
Esophageal cancer is one of the most lethal cancers worldwide because of its rapid progression and poor prognosis. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are two major subtypes of esophageal cancer. ESCC predominantly affects African and Asian populations, which is closely related to chronic smoking and alcohol consumption. EAC typically arises in Barrett's esophagus with a predilection for Western countries. While surgical operation and chemoradiotherapy have been applied to combat this deadly cancer, molecularly targeted therapy is still at the early stages. With the development of large-scale next-generation sequencing, various genomic alterations in ESCC and EAC have been revealed and their potential roles in the initiation and progression of esophageal cancer have been studied. Potential therapeutic targets have been identified and novel approaches have been developed to combat esophageal cancer. In this review, we comprehensively analyze the genomic alterations in EAC and ESCC and summarize the potential role of the genetic alterations in the development of esophageal cancer. Progresses in the therapeutics based on the different tissue types and molecular signatures have also been reviewed and discussed.
ABSTRACT
Adipocytic tumours are the most common soft tissue tumours and are frequently encountered in the routine practice. Vast majority of adipocytic tumours are benign lipomatous tumours, but there are other rare heterogenous adipocytic neoplasms which can create diagnostic difficulties. It can vary from a locally recurrent tumour to a highly malignant type carrying a poor prognosis. The classification of adipocytic tumours has evolved in the last few decades due to advances in the understanding of pathogenetic basis that also provides a greater opportunity for the development of new treatment modalities. So, with the use of ancillary diagnostic tests, definite diagnostic criteria have been established, which have been described in WHO 2013 classification and recently a newer terminology have been described, which is Atypical Spindle Cell Lipomatous Tumour and it is considered as a separate entity based on its morphology and molecular studies. Lipomas are the most common benign adipocytic tumours and the less common tumours are lipoblastoma, angiolipoma, spindle cell/pleomorphic lipoma, myolipoma, chondroid lipoma, lipomatosis of nerve and hibernoma. Well differentiated liposarcomas/ atypical lipomatous tumours are locally aggressive adipocytic neoplasms that do not metastasize. More aggressive liposarcomas include myxoid liposarcoma, pleomorphic liposarcoma and dedifferentiated liposarcomas. Within a time period of 6 months we received 362 adipocytic tumours in the department of Pathology, of which 354 were benign and 8 cases were intermediate (locally aggressive) and malignant which includes atypical spindle cell lipomatous tumour, atypical lipomatous tumour/ well differentiated liposarcoma, myxoid liposarcoma and dedifferentiated liposarcoma. The cases of atypical lipomatous tumour and atypical spindle cell lipomatous tumour, its histological and molecular basis will be discussed along with this review of literature. Atypical spindle cell lipomatous tumours are seen usually in the subcutaneous location with a wide anatomic distribution and more commonly seen in the adults of 6th decade. Gross appearance ranges from yellowish to whitish depending on the amount of adipocytic and fibrous differentiation. Microscopic study shows a hypercellular to a hypocellular lesion with mild to moderately atypical spindle cells, adipocytes, lipoblast, and occasional bizarre, hyperchromatic cells. The stroma can be myxoid or collagenous. Mitotic figures are sparse without any tumour necrosis. Rare heterologous differentiation and different growth patterns have been describedincluding solitary fibrous tumour (SFT) like pattern, angiofibroma like pattern, myxoid liposarcoma like pattern and pericytic pattern. Immunohistochemistry studies show variable expression of CD34, S100 and desmin. Molecular studies identified a characteristic loss of nuclear RB gene expression with deletion of 13q14. The indolent behaviour of atypical spindle cell lipomatous tumour, with very low recurrence rate, no risk of dedifferentiation and no reported distant metastasis / death from disease, highlights the importance of distinguishing it from atypical lipomatous tumour/well differentiated liposarcoma, in order to avoid aggressive surgical resections. So atypical spindle cell lipomatous tumour is now considered as an independent entity rather than a morphological variant of atypical lipomatous tumour.
ABSTRACT
Cancer development is accompanied by genetic events like losses, gains and amplification of certain chromosome regions or alterations of chromatin structure. Array-based CGH (Array-CGH) is a highly comprehensive, sensitive and fast technique to allow investigation of general changes in target oncogenes and tumor suppressor genes. Recently, the prevalence of colon cancer is rapidly increasing in Korea and now it is the fourth leading cause of cancer death. So, the purpose of this study is to examine genomic alterations in colon cancer cell lines and to search novel genes which might be related to the development of colon cancer. In this study, genomic alterations are analyzed by using array-CGH in three colon cell lines from Korean, SNU-81, SNU-407 and SNU-1047. We observed numerous chromosomal imbalances from all cell lines. The common chromosomal gains were observed in 1p36.33, 1q22, 1q32.1, 2q35, 8p12, 8q22.3, 14q32.33, 16p13.3, and 16q24. Common chromosomal losses were found in 4q22.1, 9q13, 14q21.1, 14q32.33, 20p12.1, Xq21.1, and Yq11.223. Gains of 1p, 2q, 8p, and 8q or losses of 4q, 14q and 20p are already known to be associated with the colon cancer development. For gene alterations, we could see gains of some genes such as ELF3 and AAMP, which were already reported to be associated with colon cancer. Also, we could find some gene alterations which were known to be associated with other cancer types. These genes were GON4L, RNPEP, TMBIM1, TIMM17A, GPBAR1, PPP1R13B and SOX8. Besides, we found alterations of new genes such as PKND and LEPROTL1. The association of these genes with colon cancer is first demonstrated here. These genes may be the novel candidate genes functioning in the development of colon cancer. In conclusion, array-CGH demonstrated the complexity of genetic aberrations in several colon cell lines. These data about the patterns of genomic alterations could be a basic step for understanding more detailed genetic events in the carcinogenesis and also provide information about possible target genes for diagnosis and treatment in colon cancer.