Editing Spindle checkpoint (section)

=== Mutated genes in cancers ===

In some cancers the genes that underlie the defects resulting in transformation are well characterized. In the hematological cancers such as multiple myeloma cytogenetic abnormalities are very common due to the inherent nature of DNA breaks needed for immunoglobulin gene rearrangement. However, defects in proteins such as MAD2 that function predominantly at the SAC also are characterized in multiple myeloma.<ref name="Diaz Rodriguez">{{cite journal | vauthors = Díaz-Rodríguez E, Álvarez-Fernández S, Chen X, Paiva B, López-Pérez R, García-Hernández JL, San Miguel JF, Pandiella A | title = Deficient spindle assembly checkpoint in multiple myeloma | journal = PLOS ONE | volume = 6 | issue = 11 | pages = e27583 | year = 2011 | pmid = 22132115 | pmc = 3223182 | doi = 10.1371/journal.pone.0027583 | bibcode = 2011PLoSO...627583D | doi-access = free }} {{open access}}</ref> Most solid tumors are also predominantly aneuploid. For colorectal cancer,  BUB1 and BUBR1 and amplification of STK15 are key regulators that have been implicated in the genomic instability resulting in cancer.<ref name="Grady2004">{{cite journal |doi= 10.1023/A:1025861527711|year=2004 |last1=Grady |first1= William M. |journal=Cancer and Metastasis Reviews|volume=23 |issue= 1–2 |pages= 11–27|title= Genomic instability and colon cancer|pmid=15000146 |s2cid=1177511 }}</ref>  In breast cancer, the genetic form characterized by the BRCA-1 gene exhibits greater levels of genomic instability than sporadic forms. Experiments showed that BRCA-1 null mice have decreased expression of the key spindle checkpoint protein MAD2 .<ref name="Wang2004">{{cite journal | vauthors = Wang RH, Yu H, Deng CX | title = A requirement for breast-cancer-associated gene 1 (BRCA1) in the spindle checkpoint | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 49 | pages = 17108–13 | date = December 2004 | pmid = 15563594 | pmc = 535394 | doi = 10.1073/pnas.0407585101 | bibcode = 2004PNAS..10117108W | doi-access = free }}</ref> For other cancers, more work is warranted to identify the causes of aneuploidy.