D. H. Kim

High performance PRAM cell scalable to sub-20nm technology with below 4F2 cell size, extendable to DRAM applications

A PRAM cell with great scalability and high speed operation capability with excellent reliability below 20nm technology was demonstrated. This has the meaning of the potential applicable to the technology area of scaling limitation of DRAM cell. We fabricated a confined PRAM cell with 7.5nm×17nm of below 4F2. In particular, Sb-rich Ge-Sb-Te phase change material was employed for high speed operation below 30nsec. The excellent writing endurance performance was predicted to maintain up to 6.5E15cycles by reset program energy acceleration. Its data retention was 4.5 years at 85°C which is enough for DRAM application.

The breakthrough in data retention time of DRAM using Recess-Channel-Array Transistor(RCAT) for 88 nm feature size and beyond

For the first time, 512 Mb DRAMs using a Recess-Channel-Array-Transistor(RCAT) are successfully developed with 88 nm feature size, which is the smallest feature size ever reported in DRAM technology with non-planar array transistor. The RCAT with gate length of 75 nm and recessed channel depth of 150 nm exhibits drastically improved electrical characteristics such as DIBL, BV/sub DS/, junction leakage and cell contact resistance, comparing to a conventional planar array transistor of the same gate length. The most powerful effect using the RCAT in DRAMs is a great improvement of data retention time. In addition, this technology will easily extend to sub-70 nm node by simply increasing recessed channel depth and keeping the same doping concentration of the substrate.

Elevated mRNA levels of DNA methyltransferase‐1 as an independent prognostic factor in primary nonsmall cell lung cancer

Despite many reports about the involvement of DNA methyltransferases (DNMTs) in human cancers, including nonsmall cell lung cancer (NSCLC), the clinicopathologic significance of DNMTs in primary NSCLC remains to be elucidated.

S-RCAT (sphere-shaped-recess-channel-array transistor) technology for 70nm DRAM feature size and beyond

For the first time, S-RCAT (sphere-shaped-recess-channel-array transistor) technology has been successfully developed in a 2Gb density DRAM with 70nm feature size. It is a modified structure of the RCAT (recess-channel-array transistor) and shows an excellent scalability of recessed-channel structure to sub-50nm feature size. The S-RCAT demonstrated superior characteristics in DIBL, subthreshold swing (SW), body effect, junction leakage current and data retention time, comparing to the RCAT structure, in this paper, S-RCAT is proved to be the most promising DRAM array transistor suitable for sub-50nm and mobile applications.

Aberrant methylation of H-cadherin (CDH13) promoter is associated with tumor progression in primary nonsmall cell lung carcinoma.

Abnormalities in the H‐cadherin gene have been reported in several human malignancies, including nonsmall cell lung carcinoma (NSCLC). Aberrant methylation of the H‐cadherin promoter also has been reported in NSCLC, but its clinical significance remains to be elucidated.

Identification of Driving ALK Fusion Genes and Genomic Landscape of Medullary Thyroid Cancer

The genetic landscape of medullary thyroid cancer (MTC) is not yet fully understood, although some oncogenic mutations have been identified. To explore genetic profiles of MTCs, formalin-fixed, paraffin-embedded tumor tissues from MTC patients were assayed on the Ion AmpliSeq Cancer Panel v2. Eighty-four sporadic MTC samples and 36 paired normal thyroid tissues were successfully sequenced. We discovered 101 hotspot mutations in 18 genes in the 84 MTC tissue samples. The most common mutation was in the ret proto-oncogene, which occurred in 47 cases followed by mutations in genes encoding Harvey rat sarcoma viral oncogene homolog (N = 14), serine/threonine kinase 11 (N = 11), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (N = 6), mutL homolog 1 (N = 4), Kiesten rat sarcoma viral oncogene homolog (N = 3) and MET proto-oncogene (N = 3). We also evaluated anaplastic lymphoma kinase (ALK) rearrangement by immunohistochemistry and break-apart fluorescence in situ hybridization (FISH). Two of 98 screened cases were positive for ALK FISH. To identify the genomic breakpoint and 5’ fusion partner of ALK, customized targeted cancer panel sequencing was performed using DNA from tumor samples of the two patients. Glutamine:fructose-6-phosphate transaminase 1 (GFPT1)-ALK and echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusions were identified. Additional PCR analysis, followed by Sanger sequencing, confirmed the GFPT1-ALK fusion, indicating that the fusion is a result of intra-chromosomal translocation or deletion. Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib. In conclusion, we found several genetic mutations in MTC and are the first to identify ALK fusions in MTC. Our results suggest that the EML4-ALK fusion in MTC may be a potential driver mutation and a valid target of ALK inhibitors. Furthermore, the GFPT1-ALK fusion may be a potential candidate for molecular target therapy.

Association of the SUV39H1 histone methyltransferase with the DNA methyltransferase 1 at mRNA expression level in primary colorectal cancer.

This study was aimed at investigating the involvement of the SUV39H1 histone methyltransferase on the epigenetic change of euchromatic promoter in colorectal cancer. We retrospectively analyzed the mRNA levels of SUV39H1 and the promoter methylation of the p14ARF, p16INK4a and HLTF genes as well as the mRNA levels of DNA methyltransferase 1 (DNMT1) in fresh frozen tissues from 219 colorectal cancer patients. The mRNA levels of the SUV39H1 and DNMT1 were assessed via quantitative real‐time PCR and the methylation profiles of the CpG islands were determined using methylation‐specific PCR. The mRNA levels of SUV39H1 and DNMT1 were elevated in 25% and 42% of 219 colorectal cancers, respectively. The hypermethylation of the p14ARF, p16INK4a and HLTF genes occurred in 36%, 51% and 34% of the patients. The elevated mRNA levels of SUV39H1 were not associated with the hypermethylation of the 3 genes. However, the mRNA levels of DNMT1 were significantly different between patients with elevated mRNA levels of SUV39H1 and those without (1.62 ± 0.84, 0.91 ± 0.81, respectively; p = 0.007). Patients with elevated mRNA levels of SUV39H1 showed a higher prevalence of DNMT1 elevation than those without (61 vs. 35%, p = 0.0008). Patients with an elevated mRNA level of SUV39H1 had a 2.71 (95% CI = 1.09–4.48, p = 0.002) times greater risk of an elevated mRNA level of DNMT1, after controlling for age and gender. In conclusion, the present study suggests that SUV39H1 is significantly associated with DNMT1, but not with euchromatic promoter methylation in colorectal cancer.

CpG island hypermethylation of E-cadherin (CDH1) and integrin α4 is associated with recurrence of early stage esophageal squamous cell carcinoma

The prognosis of esophageal squamous cell carcinoma (ESCC) patients remains very poor, which is partially due to a high rate of recurrence. This study was aimed at identifying a recurrence‐associated epigenetic prognostic marker in patients with ESCC. We retrospectively analyzed the CpG island hypermethylation of the p16, Wif‐1, sFRP1, integrin α4, CDH1, DAP kinase and RARβ2 genes in 251 ESCCs. The methylation status was determined by methylation‐specific PCR. Hypermethylation was detected in 52% for p16, 25% for RARβ2, 43% for CDH1, 21% for integrin α4, 57% for sFRP1, 38% for DAP kinase and 35% for Wif‐1. Recurrence was observed in 131 (52%) of the 251 cases. For stage I cancers, CDH1 methylation was associated with a high risk of recurrence (OR = 5.26, 95% CI = 1.48–18.67; p = 0.01) and a poor recurrence‐free survival after surgery (HR = 3.13, 95% CI = 1.21–8.09; p = 0.02). The hazard of failure after recurrence was about 13.17 (95% CI = 2.46–70.41; p = 0.003) times higher in patients with Wif‐1 methylation than in those without. For stage II cancers, integrin α4 methylation was associated with an increased risk of recurrence (OR = 3.03, 95% CI = 1.09–8.37; p = 0.03) and a poor recurrence‐free survival (HR = 2.12, 95% CI = 1.13–3.98; p = 0.03). In conclusion, the present study suggests that hypermethylation of CDH1 and integrin α4 genes may be used as recurrence‐associated prognostic indicators in stage I and stage II ESCCs, respectively.

The excellent scalability of the RCAT (recess-channel-array-transistor) technology for sub-70nm DRAM feature size and beyond

The technology innovation for extending the RCAT structure to the sub-70nm DRAM is presented. The new technology overcomes the problems induced by shrinkage of the RCAT structure and meets the requirements for the next generation DRAMs, such as high speed and low power performance. The technology roadmap down to the 50nm DRAM feature size of the RCAT development is presented.

A mechanically enhanced storage node for virtually unlimited height (MESH) capacitor aiming at sub 70nm DRAMs

Fully reliable lean-free stacked capacitor, with the meshes of the supporter made of Si/sub 3/N/sub 4/, has been successfully developed on 80nm COB DRAM application. This novel process terminates persistent problems caused by mechanical instability of storage node with high aspect ratio. With Mechanically Enhanced Storage node for virtually unlimited Height (MESH), the cell capacitance over 30fF/cell has been obtained by using conventional MIS dielectric with an equivalent 2.3nm oxide thickness. This inherently lean-free capacitor makes it possible extending the existing MIS dielectric technology to sub-70nm OCS (one cylindrical storage node) DRAMs.