Probes for INS

 Background: ASPM is a newly reported stem cell marker and plays important roles in mitosis, cell cycle and tumorigenesis. It links with poor clinical prognosis in various tumors. However, the clinical significance of ASPM in colonic adenocarcinoma (CA) has not been fully studied. The purpose of this study was to investigate if ASPM is correlated with the clinicopathological features of CA. Methods: Primary CA tissue, adenoma and the matched normal mucosa from 99 patients, were detected using immunohistochemical analysis by primary antibodies against ASPM. Meanwhile, 20 CAs and 20 liver metastatic cases were examined by RNA in situ hybridization (RNAscope). To assess the clinical relevance of ASPM, we analyzed the survival follow-up information. Results: ASPM was found only in single cells in the base of normal colon mucosal crypts. But the expression of ASPM was detected high in colonic adenomas (49.5%, 49/99), and significantly higher in CA (56.6%, 56/ 99, P<0.001). In CAs, ASPM expression was more intense in stage III and IV than II and I stage patients (P=0.03), and positively correlated with lymph node metastasis (P=0.03), but not with the age at diagnosis, gender and histological grade (P>0.05). We also analyzed the survival follow-up information, the data showed that ASPM-positive expression was correlated with a shorter disease-free survival (DFS) time, the average DFS time of patients with ASPM positive and negative expression was 62.79±2.32 months and 71.30±2.72 months, respectively, and there was no statistical significance between the two groups (P>0.05). The results of ASPM mRNA measurement by RNAscope revealed ASPM mRNA expression was higher in primary CA than that in metastatic liver CA (P<0.001). Conclusions: ASPM might play an important role in colonic carcinogenesis and be a potential marker in predicting prognosis of CA. 

Alterations in genes that regulate brain size may contribute to both microcephaly and brain tumor formation. Here, we report that Aspm, a gene that is mutated in familial microcephaly, regulates postnatal neurogenesis in the cerebellum and supports the growth of medulloblastoma, the most common malignant pediatric brain tumor. Cerebellar granule neuron progenitors (CGNPs) express Aspm when maintained in a proliferative state by sonic hedgehog (Shh) signaling, and Aspm is expressed in Shh-driven medulloblastoma in mice. Genetic deletion of Aspm reduces cerebellar growth, while paradoxically increasing the mitotic rate of CGNPs. Aspm-deficient CGNPs show impaired mitotic progression, altered patterns of division orientation and differentiation, and increased DNA damage, which causes progenitor attrition through apoptosis. Deletion of Aspm in mice with Smo-induced medulloblastoma reduces tumor growth and increases DNA damage. Co-deletion of Aspm and either of the apoptosis regulators Bax or Trp53 (also known as p53) rescues the survival of neural progenitors and reduces the growth restriction imposed by Aspm deletion. Our data show that Aspm functions to regulate mitosis and to mitigate DNA damage during CGNP cell division, causes microcephaly through progenitor apoptosis when mutated, and sustains tumor growth in medulloblastoma.