Study Links Sarcoma To Genetic Mutations

Cancer is more complex than we think. Australian scientists have recently taken a leap forward in cracking the enigma of cancer and its link with the DNA code. In a multi-country new study, the researchers have uncovered 72 gene variants which increase an individual’s likelihood of developing sarcoma, a rare form of bone and soft tissue cancer.

The researchers from Garvan Institute of Medical Research, Australia, presented the pioneering finding in an International Sarcoma Kindred Study (ISKS) which is an Australian-led international consortium, working at establishing a genetic link with sarcoma. The findings of this one of a kind study for sarcoma was also published in the online journal The Lancet Oncology on 5th August.

Sarcomas are cancers of connective tissues which have a high prevalent in children and young adults. This rare cancer also qualifies as the third leading cause of disease-related death in children and young adults in Australia. In addition to this, the severity of this cancer increasingly affects the health of cancer survivors who are prone to having a cancer relapse.

Crucial in its findings, the study recruited 1,162 sarcoma patients and their genome was sequenced to investigate into the genetic aberrations that contribute towards increased risk of this life-limiting disease.

A gene panel consisting of 72 gene variants was used to identify the mutations which showed a direct association to sarcoma cancer. In the targeted exon sequencing, 1,114 blood samples and 48 saliva samples were collected and these samples were compared against the DNA samples of 6,545 Caucasian control group.

Cancer Is A Multi-Gene Mutational Disease

After this genetic analysis, the presence of gene mutations in ERCC2, ATR, ATM, TP53 and BRACA2 genes in a majority of cancer patients was found to increase their vulnerability of developing cancer, in the first place. This also led us to a better understanding of how underlying genetics work in causing cancer not by just one-point mutation but polygenic mutations.

Amongst these genes, ERCC2 (excision repair 2, TFIH core complex helicase subunit) gene encodes proteins that work as a transcription factor which also helps repair damaged DNA, under normal working condition. ATR (serine/threonine kinase) is also a gene which regulates cell cycle for replication and helps in DNA damage repair. ATM (ATM serine/threonine kinase) gene encodes a protein which regulates the rate of cell growth and division. TP53 is an abbreviated gene name for tumor protein p53 gene which encodes protein that suppresses tumor production under normal condition. Similarly, BRCA2 is a DNA repair associated gene which also encodes a protein which works as a tumor suppressor protein in a person who does not suffer from cancer.

Genetic mutations in all these above mentioned genes had a significant role in increasing the chances of cancer in young people.

The risk was further magnified in people who were carriers of more than one genetic mutations and the risk continued to multiply with every additional mutation. This multiple-gene effect on cancer was in itself a crucial finding.

In this regard, the study-leader Professor David Thomas, Head of the Kinghorn Cancer Centre and the Cancer Division of the Garvan Institute of Medical Research, “This is the first time — in any cancer — that anyone has quantified the effect of multiple rare genetic mutations on cancer risk.”

He added that until now the scientists and oncology experts have been primarily focusing on single gene variants in connection to cancer risks but with the emergence of this study, a complex genetic pattern contributing towards cancer has been revealed. He continued to say that now that complex genetic patterns are observed, the landscape of genetic determination of cancers will be transformed all at once.

He added, “These previously invisible effects are at least as large as the impact of mutations in the p53 gene itself, which is currently the strongest known genetic cause of sarcoma.”

New Avenues For Cancer Treatment

Starting from this study the personalized risk management and treatment modalities will become part of clinical practices and surviving through cancer will become a reality.

For instance, Prof Thomas added that if a mutated ERCC2 gene is present in a patient than the clinicians will know that chemotherapy is not the right option and they will move on to alternate treatment options.

Another researcher Dr Mandy Ballinger said that the research in terms of sarcoma has been very limited and now that a hereditary link has come into play, the clinical practices in diagnosing and treating sarcomas will improve.

Earlier, an individual’s risk of sarcoma was never predicted but now the scientists are fascinated by the endless preventive diagnosis possibilities that this study promises to provide in near future.

Excited about the future of genetics and cancer medicine, Dr Ballinger concluded it aptly by saying, “We have only scratched the surface of cancer’s genetic underpinnings. Ultimately, we want to identify the entire set of genetic mutations that affect the risk of developing this devastating cancer.”

A new avenue in cancer research has certainly opened up from this study and the role of genetics is increasingly becoming evident. Let’s hope that in coming future, science can help people battle against this debilitating disease.

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