Translocation t(6;14) as the Sole Chromosomal Abnormality in Adenoid Cystic Carcinoma of the Base of Tongue

We present an adenoid cystic carcinoma of the base of tongue in a 48-year-old male with a restricted chromosomal alteration by cytogenetic and spectral karyotypic analysis (SKY). SKY and G-banding analyses identified the t(6;14)(q25;q13) as the sole structural aberration in all metaphases analyzed. This finding supports a critical role for this event in the development of this tumor. The implications of chromosome 6q translocation in this case and in previously reported adenoid cystic carcinomas are highlighted and discussed.     

Amplification of MGC2177, PLAG1, PSMC6P, and LYN in a malignant mixed tumor of salivary gland detected by cDNA microarray with tyramide signal amplification

Gene amplifications have been observed in many different tumor cells, and many of these changes are related to tumor pathogenesis. Comparative genomic hybridization (CGH) using metaphase chromosomes can detect changes in chromosome copy number with a resolution of 10-20 Mb. Current advances in CGH analysis in a microarray format allow us to refine such changes down to the gene level. We applied microarray technology to detect novel gene amplification in a malignant mixed tumor of salivary gland. Besides detecting previously known gene amplifications (MDM2 and MYC), we identified four other highly amplified genes located at 8q11.2 approximately q13: MGC2177, PLAG1, PSMC6P, and LYN. The amplification was further validated with real-time quantitative polymerase chain reaction.     

Multicolor spectral karyotyping of serous ovarian adenocarcinoma.

We applied multicolor spectral karyotyping (SKY) to decipher the chromosomal complexity of a panel of seven cell lines and four primary tumors derived from patients with high‐grade serous adenocarcinoma of the ovary. By this method we identified a total of 188 unbalanced translocations, nine reciprocal translocations [t(2;15)(q13;q23), t(7;17) (q32;q21), t(8;22)(p11;q11), t(8;22) (q24;q13), t(10;19) (q24;q13.2), t(11;19) (q13;p11), t(12;21)(q13;q22),t(18;20) (q?11;q?11), t(18;22)(q?11;q?13)], 6 isochromosomes [i(1q), i(7q), i(8q), i(9p), i(17q), i(21q)], and 23 deletions. By detailed mapping of rearrangement breakpoints, it was possible to identify several recurring breakpoint clusters at chromosomal bands 1p36, 2p11, 2p23, 3p21, 3q21, 4p11, 6q11, 8p11, 9q34, 10p11, 11p11, 11q13, 12p13, 12q13, 17q21, 18p11, 18q11, 20q11, and 21q22. Recurrent interstitial deletion of chromosomal bands 8p11, 11p11, and 12q13 and a recurrent unbalanced translocation—der(6)t(6;8)(q11;q11)—were also identified. In addition, a homogeneously staining region localized in one cell line to 11q13 was found using SKY to be derived from genetic material originating from chromosome 12. Subsequent comparative genomic hybridization (CGH) studies on this tumor revealed the amplification of DNA sequences derived from the short arm of chromosome 12 at the 12p11.2 region. These studies demonstrate the power of SKY, CGH, and G‐banding to resolve the full spectrum of chromosomal rearrangements in serous ovarian adenocarcinoma. © 2002 Wiley‐Liss, Inc.     

The Foot and Mouth Disease Virus Type O Outbreak of 1992 Is Not Related to Vaccine Strain (O/R2/75)

Vaccination is the only pragmatic approach to control foot and mouth disease in India. Strict quality control measures are essential to supply potent vaccine to the field application, in addition to monitoring the performance of the vaccine in the field. During the process of monitoring, an outbreak of FMD in vaccinated animals caused by type “O” virus in Tanjavur district of Tamil Nadu and a type “O” virus from unvaccinated herd of Karnataka were studied. Field isolates and vaccine virus were sequenced and analyzed. Data indicated that the virus from the outbreak in vaccinated cattle was a variant which could escape neutralization by antibodies against vaccine virus. This revised version was published online in August 2006 with corrections to the Cover Date.     

Identification of novel prognosticators of outcome in squamous cell carcinoma of the head and neck.

PURPOSE: The goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: We assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate chi(2) statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than.15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the chi(2) approximation of the final model by MCS. RESULTS: CGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P =.0009 to P =.01). CONCLUSION: HNSCC contains a complex pattern of chromosomal aberrations. A sequential approach to control for multiple comparisons and effect of confounding variables allows the identification of clinically relevant aberrations. The significance of each individual abnormality merits further consideration.     

Amplification and over‐expression of MAP3K3 gene in human breast cancer promotes formation and survival of breast cancer cells

Gene amplifications in the 17q chromosomal region are observed frequently in breast cancers. An integrative bioinformatics analysis of this region nominated the MAP3K3 gene as a potential therapeutic target in breast cancer. This gene encodes mitogen‐activated protein kinase kinase kinase 3 (MAP3K3/MEKK3), which has not yet been reported to be associated with cancer‐causing genetic aberrations. We found that MAP3K3 was amplified in approximately 8–20% of breast cancers. Knockdown of MAP3K3 expression significantly inhibited cell proliferation and colony formation in MAP3K3‐amplified breast cancer cell lines MCF‐7 and MDA‐MB‐361 but not in MAP3K3 non‐amplified breast cancer cells. Knockdown of MAP3K3 expression in MAP3K3‐amplified breast cancer cells sensitized breast cancer cells to apoptotic induction by TNFα and TRAIL, as well as doxorubicin, VP‐16 and fluorouracil, three commonly used chemotherapeutic drugs for treating breast cancer. In addition, ectopic expression of MAP3K3, in collaboration with Ras, induced colony formation in both primary mouse embryonic fibroblasts and immortalized human breast epithelial cells (MCF‐10A). Combined, these results suggest that MAP3K3 contributes to breast carcinogenesis and may endow resistance of breast cancer cells to cytotoxic chemotherapy. Therefore, MAP3K3 may be a valuable therapeutic target in patients with MAP3K3‐amplified breast cancers, and blocking MAP3K3 kinase activity with a small molecule inhibitor may sensitize MAP3K3‐amplified breast cancer cells to chemotherapy. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Granulocytic sarcoma presenting as pneumonia in a child with t(8;21) acute myelogenous leukemia: diagnosis by fluorescent in situ hybridization

Granulocytic sarcoma is a soft tissue collection of leukemic cells. The authors describe a 4-year-old boy with M2 acute myelogenous leukemia (AML) who presented with fever, mild nonproductive cough, and hematemesis. Although he was initially diagnosed with nodular pneumonia, rapid resolution of a pulmonary infiltrate following induction chemotherapy was suggestive of a pulmonary granulocytic sarcoma. Interphase fluorescent in situ hybridization (FISH) of the lung biopsy specimen for the t(8;21)(q22;q22) translocation confirmed the retrospective diagnosis of a well-differentiated pulmonary granulocytic sarcoma. Pulmonary granulocytic sarcomas may be underrecognized in children with AML; this may delay anti-leukemic therapy and may lead to ineffective therapy if misdiagnosed as pneumonia.