The team examined all the genes in the genomes of 100 cases ofbreast cancer. The mutated cancer-causing genes were different indifferent cancer samples, indicating that breast cancer isgenetically very diverse. Understanding the consequences of thisdiversity will be important in progressing towards more rationaltreatment. Changes to DNA lie behind all cases of cancer. |
Cancer develops as aresult of mutations -- called somatic mutations -- that areacquired during a person's lifetime. Driver mutations, which occurin cancer genes, are a small subset of somatic mutations that drivethe development of cancer. "Breast cancer is the most common cancer in women,"explains Dr Patrick Tarpey, first author from the Wellcome TrustSanger Institute. "To identify new cancer genes that lead tothe development of breast cancer, we searched for driver mutationsin over 21,000 genes, and found evidence for nine new cancer genesinvolved in the development of this cancer." These genome analyses provide a direct survey of the landscape ofdriver mutations in breast cancer. The team found driver mutationswere present in at least 40 different cancer genes.
Most individualcancers had different combinations of mutated cancer genes,demonstrating the substantial genetic diversity in breast cancer. "In 28 cases we found only a single driver, but the maximumnumber of driver mutations in an individual cancer was six,"says Professor Mike Stratton, lead author and Director of theWellcome Trust Sanger Institute. "We found that breast cancercan be caused by more than 70 different combinations of mutations. "If we consider three breast cancers, each with four drivermutations: they might share none of those driver mutations -- soeach is a different genetic 'animal'. They are different cancersdriven by different genes.
We need to classify them as carefully aswe can. This study is a step towards that goal." "One of the most striking things about breast cancer is how itprogresses differently in each patient and how each patientresponds differently to therapy," explains Dr Andy Futreal,until recently, Head of Cancer Genomics at the Wellcome TrustSanger Institute and currently an Honorary Faculty Member at theInstitute. "Our results can help us to understand thesedifferences." Our genomes are scarred by decades of continual assault that leavemutations scattered though our DNA. This is the most comprehensivestudy thus far of mutations in breast cancers, discovering nine newmutated genes that cause breast cancer, and revealing the fulldiversity of the driving events that convert normal breast cellsinto breast cancers.
"The picture is certainly more complicated than we would havewanted, but as with many other things knowledge is our strongestweapon. These comprehensive insights reveal the faulty wiring ofthe cellular circuit board that causes cells to behave as cancers.Understanding our enemy at this level of detail will allow us totake more rational approaches to therapy, to understand why somecancers respond to drugs and others do not, and direct us to newvulnerabilities to be exploited in new treatments," addsProfessor Stratton.
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