Cancer Genetics RSS feed: Current Issue. The aim of Cancer Genetics is to publish high quality scientific papers on the cellular, genetic and molecular aspects of cancer, including cancer predisposition and clinical diagnostic applications. Specific areas of interest include descriptions of new chromosomal, molecular or epigenetic alterations in benign and malignant diseases; novel laboratory approaches for identification and characterization of chromosomal rearrangements or genomic alterations in cancer cells; correlation of genetic changes with pathology and clinical presentation; and the molecular genetics of cancer predisposition. To reach a basic science and clinical multidisciplinary audience, we welcome original full-length articles, reviews, meeting summaries, brief reports, and letters to the editor. http://www.cancergeneticsjournal.org/?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. All rights reserved. Cancer Genetics2210-77622054April 2012 © 2012 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.cancergeneticsjournal.org/article/PIIS2210776212001081/abstract?rss=yesCover 110.1016/S2210-7762(12)00108-1Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7OFCOFChttp://www.cancergeneticsjournal.org/article/PIIS2210776212001093/abstract?rss=yesEditorial Board10.1016/S2210-7762(12)00109-3Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7IFCIFChttp://www.cancergeneticsjournal.org/article/PIIS2210776212000531/abstract?rss=yesAdrenocortical tumors (ACTs) are common, and most are benign adrenocortical adenomas (ACAs). Malignant adrenocortical carcinoma (ACC) is a rare tumor type and is observed at the rate of one or two cases per million annually. ACTs are classified as either ACAs or ACCs by histopathologic methods that are based on nine Weiss scoring criteria, including the nuclear grade, mitotic rate, presence of necrosis, and others. In this review, we describe the findings of studies that have examined the molecular basis of ACTs, and we compare transcriptome analysis with other diagnostic approaches. ACTs are occasionally difficult to classify. Therefore, molecular techniques, such as microarray analysis, have recently been applied to overcome some of these diagnostic problems. We also discuss the likelihood of the diagnosis and discernment between ACAs and ACCs based on the molecular tests. To show the recent progress in understanding the etiology of ACTs, we highlight the relationship between genetic analysis and transcriptome analysis. We attempt to understand the role of abnormal cell growth and steroid hormone secretion. Genetic and transcriptome analyses have improved our understanding of ACTs considerably, yet many unanswered questions remain.The molecular basis of adrenocortical cancerTomasz Lehmann, Tomasz Wrzesinski10.1016/j.cancergen.2012.02.009Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Review131137http://www.cancergeneticsjournal.org/article/PIIS2210776212000038/abstract?rss=yesThe estrogen receptor (ER) is a well-known predictor of breast cancer response to endocrine therapy. ER+ progesterone receptor (PR)− breast tumors have a poorer response to endocrine therapy and a more aggressive phenotype than ER+PR+ tumors. A comparative genomic hybridization array technique was used to examine 25 ER+PR+ and 23 ER+PR− tumors. Tissue microarrays composed of 50 ER+PR+ and 50 ER+PR− tumors were developed to validate the comparative genomic hybridization array results. The genes of interest were analyzed by fluorescence in situ hybridization. The ER+PR− group had a slightly different genomic profile when compared with ER+PR+ tumors. Chromosomes 17 and 20 contained the most overlapping gains, and chromosomes 3, 8, 9, 14, 17, 21, and 22 contained the most overlapping losses when compared with the ER+PR+ group. The gained regions, 17q23.2-q23.3 and 20q13.12, and the lost regions, 3p21.32-p12.3, 9pter-p13.2, 17pter-p12, and 21pter-q21.1, occurred at different alteration frequencies and were statistically significant in the ER+PR− tumors compared with the ER+PR+ tumors. ER+PR− breast tumors have a different genomic profile compared with ER+PR+ tumors. Differentially lost regions in the ER+PR− group included genes with tumor suppressor functions and genes involved in apoptosis, mitosis, angiogenesis, and cell spreading. Differentially gained regions included genes such as MAP3K3, RPS6KB1, and ZNF217. Amplification of these genes could contribute to resistance to apoptosis, increased activation of the PI3K/Akt/mTOR pathway, and the loss of PR in at least some ER+PR− tumors.Are ER+PR+ and ER+PR− breast tumors genetically different? A CGH array studyAlma Carracedo, Marta Salido, Josep M. Corominas, Federico Rojo, Bibiana I. Ferreira, Javier Suela, Ignasi Tusquets, Cristina Corzo, Marcel Segura, Blanca Espinet, Juan C. Cigudosa, Montserrat Arumi, Joan Albanell, Sergi Serrano, Francesc Solé10.1016/j.cancergen.2012.01.001Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Original Articles138146http://www.cancergeneticsjournal.org/article/PIIS2210776212000051/abstract?rss=yesThe identification of molecular markers for diagnosis, treatment, and prognosis is a significant issue in the management of patients with gastric cancer. We compared the expression profiles of 23 gastric cancers and 22 normal gastric tissues using cDNA microarrays. We divided the samples into two sets, 11 pairs as a training set and 12 unpaired gastric cancer and 11 unpaired normal gastric tissues as a test set. We selected significant genes in the training set and validated the significance of the genes in the test set. We obtained 238 classifier genes that showed a maximum cross-validation probability and clear hierarchical clustering pattern in the training set, and showed excellent class prediction probability in the independent test set. The classifier genes consisted of known genes related to the biological features of cancer and 28% unknown genes. We obtained genome-wide molecular signatures of gastric cancer, which provides preliminary exploration data for the pathophysiology of gastric cancer.Identification of differentially expressed genes in gastric cancer by high density cDNA microarraySong-Nan Zhang, Hong-Hua Sun, Yong-Min Jin, Long-Zhen Piao, De-Hao Jin, Zhen-Hua Lin, Xiong-Hu Shen10.1016/j.cancergen.2012.01.003Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Original Articles147155http://www.cancergeneticsjournal.org/article/PIIS2210776212000403/abstract?rss=yesBladder cancer is a common malignancy in developing countries in which bladder infection with the parasite Schistosoma haematobium is prevalent. Several epidemiological, histopathological, and clinical characteristics of schistosoma-associated bladder cancer suggest that it is distinct from bladder cancer seen in other places in the world. The aim of this study was to extend establishing the cytogenetic profile of this type of malignancy in advanced and metastatic cases, and to demonstrate its relation to the end results of systemic therapy. Fluorescence in situ hybridization was applied to interphase nuclei to detect numerical chromosome changes in 41 patients with bladder cancer. Numerical chromosome aberrations were detected in 27 of 41 cases (66%). In 17 (41%) cases, a gain of chromosome 7 was observed, while losses in chromosomes 9 and 17 were detected in 20 (49%) and 18 (44%) cases, respectively. Loss of chromosome Y was detected in 7 of the 32 male patients included in this study (22%). There was a statistically significant association between stage of the disease and overall survival; Bajorin score and time to disease progression and overall survival; and between response to systemic therapy and time to disease progression and overall survival. The only chromosomal abnormality that had a significant relationship with overall survival was the gain of chromosome 4. When the genetic basis of schistosoma-associated bladder cancer is fully understood, new diagnostic and therapeutic strategies could be developed, which in turn may promote better clinical management and survival.Cytogenetic profile of locally advanced and metastatic schistosoma-related bladder cancer and response to chemotherapyMagdy Sayed Aly, Hussein Mostafa Khaled, Mohamed Emara, Tarek D. Hussein10.1016/j.cancergen.2012.01.011Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Original Articles156162http://www.cancergeneticsjournal.org/article/PIIS2210776212000440/abstract?rss=yesUridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1) is the key hepatic detoxification enzyme involved in the biotransformation of many carcinogens implicated in the development of colon, breast, and prostate cancers in humans. A polymorphism in the UGT1A1 promoter containing a TA-repeat element [(TA)5–8TAA] is involved in the modulation of UGT1A1 transcriptional activity. The wild-type activity is associated with the (TA)6TAA allele (UGT1A1*1), whereas UGT1A1 expression decreases with the increase of the TA-repeat number. We hypothesize that the low-activity allele UGT1A1*28 with seven TA repeats is associated with a higher risk for colorectal cancer. Our study involved 168 patients with histopathologically confirmed sporadic colorectal cancer and a control group of 96 individuals with no personal history of colorectal cancer. We detected a higher frequency of UGT1A1*28 than the wild-type UGT1A1*1 allele in colorectal cancer patients as compared with that of controls (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.07–2.26, P = 0.021). The frequency of genotypes containing the UGT1A1*28 allele in the homozygous or heterozygous state was significantly higher than the frequency of the wild-type UGT1A1*1/*1 genotype in colorectal cancer patients as compared with controls (OR = 2.0, 95% CI = 1.19–3.34, P = 0.007). Our results indicate that the UGT1A1*28 allele is a risk factor for colorectal cancer in the Macedonian male population, whereas no significant risk was detected among women.Promoter length polymorphism in UGT1A1 and the risk of sporadic colorectal cancerMarija Hiljadnikova Bajro, Toni Josifovski, Milco Panovski, Nikola Jankulovski, Aleksandra Kapedanovska Nestorovska, Nadica Matevska, Natalija Petrusevska, Aleksandar J. Dimovski10.1016/j.cancergen.2012.01.015Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Original Articles163167http://www.cancergeneticsjournal.org/article/PIIS2210776212000464/abstract?rss=yesBladder cancer is frequently associated with chromosomal abnormalities, and the complexity of karyotypes increases with tumor progression. The murine model MB49 is one of the most widely studied models of bladder cancer. We developed the invasive cell line MB49-I by successive in vivo passages of MB49 primary tumors. Because little is known about the chromosomal alterations of this model, our goal was to perform cytogenetic analyses of the MB49 and MB49-I lines. The karyotypes of both lines were analyzed by G-banding and fluorescence in situ hybridization techniques. Both lines were composed of two cell subpopulations, a diploid population, which was found mainly in the MB49 line, and the tetraploid population, which was found mainly in the MB49-I line. A translocation between chromosomes 5 and 9 and an isochromosome of chromosome 19 were observed in the subpopulations of both lines. New structural abnormalities and additional chromosomal imbalances were detected in the MB49-I line. Tumor progression in the MB49/MB49-I model was associated with a selection of polyploid cells with accompanying chromosomal abnormalities. This model may be advantageous for the study of the genetic changes associated with the progression of bladder cancer.Cytogenetic characterization of the murine bladder cancer model MB49 and the derived invasive line MB49-IVictoria T. Fabris, Catalina Lodillinsky, María Betina Pampena, Denise Belgorosky, Claudia Lanari, Ana María Eiján10.1016/j.cancergen.2012.02.002Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Original Articles168176http://www.cancergeneticsjournal.org/article/PIIS2210776212000415/abstract?rss=yesNevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by a very wide spectrum of clinical signs and symptoms. Here, we report an unusual case of NBCCS in a 38-year-old man with an early onset of clinical signs and symptoms and an associated unicystic ameloblastoma, histopathologically showing basaloid differentiation and intraluminal growth. The odontogenic tumor was surgically enucleated and recurred at the follow-up at 14 months. The proband and his child were identified as gene carriers of the novel K729M PTCH1 missense mutation; other first- and second-degree relatives presented clinical features of NBCCS. Only five other cases of association between ameloblastoma and NBCCS have been reported so far, suggesting that PTCH1 missense mutation might take part in the pathogenesis of keratocystic odontogenic tumors (KCOTs) as well as ameloblastomas.Unicystic ameloblastoma associated with the novel K729M PTCH1 mutation in a patient with nevoid basal cell carcinoma (Gorlin) syndromeGiovanni Ponti, Annamaria Pollio, Michele Davide Mignogna, Giovanni Pellacani, Lorenza Pastorino, Giovanna Bianchi-Scarrà, Carmela Di Gregorio, Cristina Magnoni, Paola Azzoni, Maurizio Greco, Stefania Seidenari10.1016/j.cancergen.2012.01.012Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Brief Communications177181http://www.cancergeneticsjournal.org/article/PIIS2210776212000452/abstract?rss=yesClear cell sarcoma (CCS) of tendons and aponeuroses is an aggressive neoplasm that is characterized by a pathognomonic translocation, t(12;22)(q13;q12), resulting in an EWSR1-ATF1 chimeric gene. We report for the first time a female patient with CCS exhibiting both EWSR1-ATF1 fusion transcripts and hereditary homozygous point mutations in introns 11 and 16 of the KIT gene. Her parents and two brothers each had heterozygous point mutations in intron 11 or intron 16 of the KIT gene. The functional significance of these germline deep intronic point mutations and their relationship to the pathogenesis of CCS are unclear. Future studies investigating KIT intron mutations in a larger cohort of CCS patients are warranted.Deep intronic point mutations of the KIT gene in a female patient with cutaneous clear cell sarcoma and her familyThilo Gambichler, Ioanna Pantelaki, Nick Othlinghaus, Rose K.C. Moritz, Ingo Stricker, Marina Skrygan10.1016/j.cancergen.2012.02.001Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Brief Communications182185http://www.cancergeneticsjournal.org/article/PIIS221077621200049X/abstract?rss=yesExtranodal NK/T lymphoma, nasal type, is an uncommon neoplasm that occurs with a higher prevalence among Asian populations and Native American populations of Central and Southern America. In Western countries, this tumor is extremely rare, accounting for less than 1.5% of all non-Hodgkin lymphomas. Cytogenetic analyses have been performed only in a limited number of cases, mainly because of technical problems related to extensive necrosis and the scarcity of clinical samples, and these have shown complex karyotypes with no specific chromosomal translocations. Here, we report the cytogenetic characterization of a clinically aggressive nasal NK/T-cell lymphoma occurring in a 40-year-old Italian male patient, in which the sole chromosome abnormality was a partial trisomy of chromosome 13.Partial trisomy of chromosome 13 as a single cytogenetic abnormality in an Italian case of nasal NK/T lymphomaSilvia Uccella, Barbara Bernasconi, Isabella Ricotti, Ilaria Proserpio, Giuseppe Calabrese, Carlo Capella, Maria Grazia Tibiletti10.1016/j.cancergen.2012.02.005Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Brief Communications186189http://www.cancergeneticsjournal.org/article/PIIS221077621200052X/abstract?rss=yesThe WT1 gene was originally identified because of its role in the pathogenesis of Wilms tumor. It encodes a transcription factor that is physiologically expressed in hematopoietic stem cells , and it is detected in peripheral blood and at higher levels in bone marrow (BM) in the healthy population . Previous research has shown it to be overexpressed in several hematopoietic tumors, including acute myeloid leukemia (AML) . AML is a neoplasm with very good response to induction chemotherapy, but a high rate of relapse is observed. Therefore, there is a drive to develop novel therapeutic strategies, and minimal residual disease (MRD) approaches have a central role in the management of these patients. WT1 is one of the molecular markers used to perform MRD assessments .Correlation of WT1 expression with the burden of total and residual leukemic blasts in bone marrow samples of acute myeloid leukemia patientsJuan Manuel Alonso-Dominguez, Maria Tenorio, Diego Velasco, Lorena Abalo, Sara Lozano, Jesus Villarrubia, Javier López-Jimenez, Silvia Grande, Rosa Ayala10.1016/j.cancergen.2012.02.008Cancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7Letter to the Editor190191http://www.cancergeneticsjournal.org/article/PIIS221077621200110X/abstract?rss=yesTable of Contents10.1016/S2210-7762(12)00110-XCancer Genetics 205, 4 (2012)2012-04-01Cancer Genetics2012-04-012054S2210-7762(11)X0015-7FrontmatterA1A2