BRCA mutation status and pathological characterization of breast cancer in Zhoushan Islands, China.

OBJECTIVE: To investigate BRCA1/2 gene mutations and their relationship with clinicopathological features in patients with breast cancer in Zhoushan Islands. METHODS: High-throughput whole-exome gene sequencing was used to detect BRCA1/2 mutations in 776 breast cancer patients in Zhoushan Islands. RESULTS: The BRCA1/2 mutation rate of breast cancer patients in Zhoushan Islands was 4.38% (34/776). BRCA1 mutations were significantly correlated with age, molecular type, and family history of breast and ovarian cancers. BRCA2 mutations were most commonly found in invasive lobular carcinoma. Moreover, the BRCA2 mutation rate of cancers with molecular type luminal B (receptor protein-tyrosine kinase [HER2]-negative) was also relatively high. CONCLUSION: The rate of BRCA1/2 mutations in breast cancer patients from Zhoushan Islands is approximately 4.38%, and BRCA1 mutation is related to age, molecular type, and family history of breast and ovarian cancers.

Knockout of OsSWEET15 Impairs Rice Embryo Formation and Seed-Setting.

We show that the knockout of a sugar transporter gene OsSWEET15 led to a significant drop in rice fertility with around half of the knockout mutant's spikelets bearing blighted or empty grains. The rest of the spikelets bore fertile grains with a slightly reduced weight. Notably, the ovaries in the blighted grains of the ossweet15 mutants expanded after flowering but terminated their development before the endosperm cellularization stage and subsequently aborted. ß- glucuronidase (GUS) and Green Fluorescent Protein (GFP) reporter lines representing the OsSWEET15 expression showed that the gene was expressed in the endosperm tissues surrounding the embryo, which supposedly supplies nutrients to sustain embryo development. These results together with the protein's demonstrated sucrose transport capacity and plasma membrane localization suggest that OsSWEET15 plays a prominent role during the caryopsis formation stage, probably by releasing sucrose from the endosperm to support embryo development. By contrast, the empty grains were probably caused by the reduced pollen viability of the ossweet15 mutants. Investigation of ossweet11 mutant grains revealed similar phenotypes to those observed in the ossweet15 mutants. These results indicate that both OsSWEET15 and OsSWEET11 play important and similar roles in rice pollen development, caryopsis formation and seed-setting, in addition to their function in seed-filling that was demonstrated previously.

Essentiality for rice fertility and alternative splicing of OsSUT1.

Sucrose-proton symporters play important roles in carbohydrate transport during plant growth and development. Their physiological functions have only been partly characterized and their regulation mechanism is largely unclear. Here we report that the knockout of a sucrose transporter gene, OsSUT1, by CRISPR-Cas9 mediated gene editing resulted in a slightly dwarf size and complete infertility of the gene's homozygous mutants. Observation of caryopsis development revealed that the endosperm of OsSUT1 mutants failed to cellularize and did not show any sign of seed-filling. Consistently, OsSUT1 was identified to express strongly in developing caryopsis of wild-type rice, particularly in the nucellar epidermis and aleurone which are critical for the uptake of nutrients into the endosperm. These results indicate that OsSUT1 is indispensable during the rice reproductive stage particularly for caryopsis development. Interestingly, OsSUT1 possesses at least 6 alternative splicing transcripts, including the 4 transcripts deposited previously and the other two identified by us. The differences among these transcripts primarily lie in their coding region of the 3' end and 3' UTR region. Real-time PCR showed that 4 of the 6 transcripts had different expressional patterns during rice vegetative and reproductive growth stages. Given the versatility of the gene, addressing its alternative splicing mechanism may expand our understanding of SUT's function substantially.