Dataset Information

Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma.

ABSTRACT: Mucinous adenocarcinoma of the salivary gland (MAC) is a lethal cancer with unknown molecular etiology and a high propensity to lymph node metastasis. Mostly due to its orphan status, MAC remains one of the least explored cancers that lacks cell lines and mouse models that could help translational and pre-clinical studies. Surgery with or without radiation remains the only treatment modality but poor overall survival (10-year, 44%) underscores the urgent need for mechanism-based therapies.We developed the first patient-derived xenograft (PDX) model for pre-clinical MAC studies and a cell line that produces aggressively growing tumors after subcutaneous injection into nude mice. We performed cytogenetic, exome, and proteomic profiling of MAC to identify driving mutations, therapeutic targets, and pathways involved in aggressive cancers based on TCGA database mining and GEO analysis.We identified in MAC KRAS (G13D) and TP53 (R213X) mutations that have been previously reported as drivers in a variety of highly aggressive cancers. Somatic mutations were also found in KDM6A, KMT2D, and other genes frequently mutated in colorectal and other cancers: FAT1, NBEA, RELN, RLP1B, and ZFHX3. Proteomic analysis of MAC implied epigenetic up-regulation of a genetic program involved in proliferation and cancer stem cell maintenance.Genomic and proteomic analyses provided the first insight into potential molecular drivers of MAC metastases pointing at common mechanisms of CSC propagation in aggressive cancers. The in vitro/in vivo models that we created should aid in the development and validation of new treatment strategies against MAC.

SUBMITTER: Panaccione A

PROVIDER: S-EPMC5335866 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma.

Panaccione Alex A Zhang Yi Y Mi Yanfang Y Mitani Yoshitsugu Y Yan Guo G Prasad Manju L ML McDonald W Hayes WH El-Naggar Adel K AK Yarbrough Wendell G WG Ivanov Sergey V SV

Oral oncology 20170109

<h4>Background</h4>Mucinous adenocarcinoma of the salivary gland (MAC) is a lethal cancer with unknown molecular etiology and a high propensity to lymph node metastasis. Mostly due to its orphan status, MAC remains one of the least explored cancers that lacks cell lines and mouse models that could help translational and pre-clinical studies. Surgery with or without radiation remains the only treatment modality but poor overall survival (10-year, 44%) underscores the urgent need for mechanism-bas ...[more]

PMID: 28249646

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Project description:Mucinous gastric carcinoma (MGC) is a rare histological subtype of gastric cancer. The clinicopathological characteristics and CT features of MGC remain controversial. This study aimed to determine the clinicopathological characteristics and CT features of MGC. We reviewed 62 patients with MGC and 104 patients with non-mucinous gastric carcinoma (NMGC), pathologically confirmed between 2003 and 2015. There are significant differences in some clinicopathological characteristics and CT features between MGC and NMGC. NMGC occurs preferentially in males and more frequently in the lower third of the stomach. Patients with MGC were characterized by larger tumor size, more advanced tumor stages (II and III) and fewer lymphatic invasions. Layered enhancement (83.3%) was the main pattern of MGC, while the most common pattern in NMGC was homogeneous enhancement (52.6%), followed by heterogonous enhancement (34.6%). The degree of enhancement of the inner layer in MGC was significantly higher than in NMGC (ΔCT of portal venous phase: 54.57 Hu vs. 47.19 Hu, P = 0.034), while the middle or outer layer in MGC was significantly less enhanced (ΔCT of portal venous phase: 19.07 Hu vs. 33.09 Hu, P <0.001). Calcifications were more common in MGC (P <0.001). ROC curves revealed that the most effective variables in distinguishing MGC and NMGC were ΔCT of the middle or outer layer in the arterial phase (AUC=0.774) and portal venous phase (AUC=0.774), followed by the attenuation value of the middle or outer layer in the unenhanced phase (AUC=0.763). Calcifications had a high specificity (98.7%) in the diagnosis of MGC. The accuracy (86.1%), sensitivity (83.3%) and specificity (87.2%) of layered enhancement in diagnosing MGC were all high. Therefore, MGC was more likely to have larger tumor size and more advanced tumor stage (II and III) than NMGC. The thicker gastric wall, layered enhancement pattern and calcification were highly suggestive CT features for differentiating MGC from NMGC.

Dataset Information

Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma.

Publications

Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma.

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