Ancestral Legacy and Cancer: Discovering a New Connection

Diagram of division of cancer cellsThe study also identified a new classification for prostate cancer.

Two pilot studies were recently published in journals temper nature And the Genomics It found genetic signatures that explain racial disparities in prostate cancer severity, particularly in sub-Saharan Africa.

Through genetic analysis of prostate cancer tumors from Australian, Brazilian and South African donors, the team has developed a new prostate cancer classification (classification scheme) and cancer drivers that not only characterize patients based on their genetic ancestry, but also predict which cancers are likely to become life-threatening, important Currently difficult.

Professor Vanessa Hayes, Professor Vanessa Hayes, a genomicist and Petrie Chair for Prostate Cancer Research at Sydney University Charles Perkins Center and College of Medicine and Health Australia. Being of African descent, or from Africa, more than doubles a man’s risk of developing prostate cancer. While genomics holds a crucial key to uncovering contributing genetic and non-genetic factors, data for Africa have so far been missing.”

Ms. Vanessa Hayes

Professor Vanessa Hayes examines a blood sample from a prostate cancer patient that was used in the study. Credit: Stephanie Zingsheim, University of Sydney

“Prostate cancer is the silent killer in our region,” said University of Pretoria Professor Rihanna Bornman, international expert in men’s health and clinical leader of the South African Prostate Cancer Study in South Africa. “We had to start with a grassroots approach, engage communities with open discussion, and create the infrastructure to include Africa in the genome revolution, while defining the true extent of prostate disease.”

More than two million cancer-specific genomic variants were identified in 183 untreated male prostate tumors residing across the three research regions using advanced whole-genome sequencing (a method for mapping the whole genetic code of cancer cells).

“We have found that Africans are affected by a greater number and spectrum of acquired genetic changes (including carcinogens), with significant implications for ancestral considerations when managing and treating prostate cancer,” said Professor Hayes.

“Using cutting-edge computational data science that allowed patterns to be identified that included all different types of cancers, we uncovered a new classification of prostate cancer that we then correlated with different disease outcomes,” said Dr. Sydney and the first author on temper nature paper.

“Integrating our unique data set with the largest public data source for European and Chinese cancer genomes allowed us, for the first time, to place the African prostate cancer genetic landscape in a global context.”

as part of her Ph.D. At the University of Sydney, Dr. Tingting Gong, first author of the book Genomics paper, painstakingly examined by genomic data for large changes in the structure of chromosomes (molecules that contain genetic information). These changes are often overlooked due to the complexity involved in computational prediction of their presence, but they are an area of ​​critical importance and contributor to prostate cancer.

“We have shown significant differences in the acquisition of complex genetic variation in tumors derived from Africa and Europe, with consequences for disease progression and new opportunities for treatment,” said Dr. Jung.

This cancer genome resource is likely the first and largest to include African data in the world.

“Through African inclusion, we have taken the first steps not only towards the globalization of precision medicine but ultimately to reduce the impact of prostate cancer mortality across rural Africa,” explains Professor Bornman.

Professor Hayes added: “One of the strengths of this study is the ability to generate and process all data through a single technical and analytical pipeline.”

Search appeared in temper nature And the Genomics The paper is part of the legacy of the late Archbishop Emeritus Desmond Tutu. He was the first African to obtain his complete genome sequence, data that will be an integral part of genetic sequencing and prostate cancer research in South Africa.

Sequencing results have been published in temper nature in 2010.

Professor Hayes said: “After being diagnosed with advanced prostate cancer at the age of 66, and succumbing to it in late December 2021, the Archbishop has been an advocate not only for prostate cancer research in South Africa, but also for the benefits that genetic medicine would offer to all people. “. .

“We hope this study will be the first step to making this happen.”

References:

“Africa-Specific Molecular Classification of Prostate Cancer” by Werachai Garatlerdsiri, Jo Jiang, Tingting Gong, Sean M Patrick, Kali Willett, Tracy Chiu, Ruth J. Kinch, Raymond Campbell, Lisa J. Horvath, Eva K.F. Chan, David C. Wedge, Rosemary Sadad, Elma Simone Broome, Shinjai PA Mutamberua, Phillip De Stricker, MS Rianna Bornman, and Vanessa M. Hayes, August 31, 2022, temper nature.
DOI: 10.1038 / s41586-022-05154-6

“Genome-wide interrogation of structural diversity reveals new oncogenic drivers specific to prostate cancer in Africa” by Tingting Gong, Werachai Garatlerdsiri, Gui Jiang, Kali Willett, Tracy Chiu, Sean M Patrick, Ruth J. Lyons, Anne-Marie Hines, Gabriella Pasqualem, Elma Simone Broome, Philip de Stricker, Chingai PA Mutamberua, Rosemary Sadad, Anthony T Papenfuss, Rihanna MS Bornman, Eva KF Chan and Vanessa M Hayes, August 31, 2022, Genomics.
DOI: 10.1186 / s13073-022-01096-w

Professor Hayes acknowledges the foresight of the Petre Foundation and donor Daniel Petre who has supported her vision of comprehensive genome research for more than eight years.

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