PPP1R7 Is a Novel Translocation Partner of CBFB via t(2;16)(q37;q22) in Acute Myeloid Leukemia.

In a subset of acute myeloid leukemia (AML) cases, the core binding factor beta subunit gene (CBFB) was rearranged via inv(16)(p13.1q22) or t(16;16)(p13.1;q22), in which the smooth muscle myosin heavy chain 11 gene (MYH11) was the partner (CBFB::MYH11). Rare variants of CBFB rearrangement occurring via non-classic chromosomal aberrations have been reported, such as t(1;16), t(2;16), t(3;16), t(5;16), and t(16;19), but the partners of CBFB have not been characterized. We report a case of AML with a complex karyotype, including t(2;16)(q37;q22), in which the protein phosphatase 1 regulatory subunit 7 gene (PPP1R7) at chromosome 2q37 was rearranged with CBFB (CBFB::PPP1R7). This abnormality was inconspicuous by conventional karyotype and interphase fluorescence in situ hybridization (FISH), thus leading to an initial interpretation of inv(16)(p13.1q22); however, metaphase FISH showed that the CBFB rearrangement involved chromosome 2. Using whole genome and Sanger sequencing, the breakpoints were identified as being located in intron 5 of CBFB and intron 7 of PPP1R7. A microhomology of CAG was found in the break and reconnection sites of CBFB and PPP1R7, thus supporting the formation of CBFB::PPP1R7 by microhomology-mediated end joining.

Identifification of a novel LDLR-RET Fusion in Lung Adenocarcinoma.

BACKGROUND: REarranged during Transfection (RET) gene fusion is one of the common oncogenic variants detectable in non-small cell lung cancer (NSCLC). The feature of most oncogenic RET gene fusion cases is that RET tyrosine kinase domain is retained in fusions and the partner gene includes a coiled-coil or LIS1 homology domain. However, only a few studies reported about the exceptional form of RET fusion in NSCLC so far. METHODS: Targeted next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) were performed on resected cancerous tissue. RESULTS: A rare form of RET fusion was identified in a 45 year-old Chinese female patient, in which exon 1-4 of LDLR fused with exon 12-21 of RET. The result was validated by FISH. CONCLUSIONS: This novel form of RET fusion in NSCLC is reported for the first time worldwide, offering a new treatment option for the patient with the possibility of using RET-selective inhibitors.

CMTR1-ALK: an ALK fusion in a patient with no response to ALK inhibitor crizotinib.

The targeted treatment of advanced non-small cell lung cancer (NSCLC) harboring genomic rearrangement of ALK is a paradigm for personalized oncology. More than 15 different ALK fusion partners have been discovered in NSCLC patients. Most of these ALK fusions responded well to the ALK inhibitor crizotinib. Crizotinib is an oral MET/ALK inhibitor used as first-line therapy in the treatment of advanced NSCLC harboring ALK rearrangement. An understanding of the mechanisms by which tumors harbor primary drug resistance or acquired resistance to targeted therapies is critical for predicting which patients will respond to a specific therapy and for the identification of additional targetable pathways to maximize clinical benefits. Cap methyltransferase 1(CMTR1) also known as hMTr1, which is translate a human cap1 2'-o-ribose methyltransferase. Here, we report the newly found ALK fusion, CMTR1-ALK, in a patient who has no response to the ALK inhibitor crizotinib. The results remind us that detecting ALK status is important, but that determining the ALK fusion type and function may be more important for patient.

Association between small heterodimer partner gene and high birth weight infants / 中华围产医学杂志

Objective To evaluate the relationship of small heterodimer partner(SHP) gene and birth weight in China. Methods A cohort study of 191 normal pregnant women was conducted. Both maternal and cord blood samples were collected. PCR-RFLP was used to detect the polymorphism of SNP-rs7504 of SHP. Results (1) The frequency of both neonatal and maternal C allele and (TC+CC) genotype increased significantly with birth weight (P=0.004, OR=3.168; P=0.005, OR=3.315; P=0.013, OR=2.495; P=0.013, OR=2.495). (2) The babies were heavier if they were C allele carrier. The average increase of birth weight was 246.3 g comparing the neonates with TC+CC genotype with those with TT genotype [(3658.7?400.94)g vs (3412.4?444.4)g, P=0.005]. The average birth weight of those maternal C allele carriers was 210.3 g heavier than those non-C allele carriers[(3628.9?405.5) g vs (3418.6?449.0 g]. (3) The fetal C allele was associated with maternal weight in pregnancy, prepregnant BMI, paternal height and weight. Women with C allele were heavier and had higher BMI without statistical significance comparing with those non-C allele carriers. Neither neonatal nor maternal SHP gene was associated with blood glucose and insulin level. (4) Multiple factors analysis showed that birth weight was related to maternal height, weight gain during pregnancy, prepregnant BMI, maternal and cord blood insulin level. After adjustment, the neonatal birth weight remained significantly correlated with cord blood SHP (P=0.0354), but not with maternal SHP gene (P=0.0711). Conclusions SHP gene is associated with newborns birth weight and may affect fetal growth.