Cancer incidence and mortality differ among individuals of different ages, but the functional consequences of genetic alterations remain largely unknown. We systematically characterized genetic alterations within protein domains stratified by affected individual's age and showed that the mutational effects on domains varied with age. We further identified potential age-associated driver genes with hotspots across 33 cancers. The candidate drivers involved numerous cancer-related genes that participate in various oncogenic pathways and play central roles in human protein-protein interaction (PPI) networks. We found widespread age biases in protein domains and identified the associations between hotspots and age. Age-stratified PPI networks perturbed by hotspots were constructed to illustrate the function of mutations enriched in domains. We found that hotspots in young adults were associated with premature senescence. In summary, we provided a catalog of age-associated hotspots and their perturbed networks, which may facilitate precision diagnostics and treatments for cancer.

Haozhe Zou

Si Li

Jiyu Guo

Luan Wen

Chongwen Lv

Feng Leng

Zefeng Chen

Mengqian Zeng

Juan Xu

Yongsheng Li

Xia Li

The American Journal of Human Genetics

CELL PRESS 已被美国人类遗传学会选中从 2008 年 1 月开始出版其首屈一指的月刊。美国人类遗传学杂志 (AJHG) 是 CELL PRESS 作为其第一个社会所有期刊的一项令人兴奋的新冒险。美国人类遗传学会 (ASHG) 和 CELL PRESS 预计 AJHG 的内容与 CELL PRESS 的 12 个标题（包括 CELL、MOLECULAR CELL、CURRENT BIOLOGY 和 IMMUNITY）之间会产生巨大的协同作用。自 1948 年成立以来，THE AMERICAN JOURNAL OF HUMAN遗传学提供了与人类遗传相关的研究和评论记录，以及遗传原理在医学和公共政策中的应用，以及分子和细胞生物学的相关领域。

The American Journal of Human Genetics (AJHG) is a premier monthly journal published by the American Society of Human Genetics (ASHG) in collaboration with CELL PRESS, starting from January 2008. This journal represents an exciting new venture for CELL PRESS as its first society-owned journal, aiming to create significant synergies with CELL PRESS's other titles, including CELL, MOLECULAR CELL, CURRENT BIOLOGY, and IMMUNITY. Since its establishment in 1948, the American Journal of Human Genetics has provided a record of research and reviews related to human genetics, as well as the application of genetic principles in medicine and public policy, alongside relevant fields of molecular and cellular biology.

《美国人类遗传学杂志》（American Journal of Human Genetics）是由美国人类遗传学会（ASHG）与CELL PRESS合作出版的月刊，自2008年1月起发行。该杂志是CELL PRESS作为其首个社会所有期刊的一项重要尝试，旨在促进与CELL PRESS旗下其他期刊（如CELL、MOLECULAR CELL、CURRENT BIOLOGY和IMMUNITY）之间的协同作用。自1948年创刊以来，《美国人类遗传学杂志》一直致力于发布与人类遗传学相关的研究和评论，涵盖遗传学原理在医学和公共政策中的应用，以及分子和细胞生物学的相关领域。

American Journal of Human Genetics

Am J Hum Genet

Pan-cancer analysis reveals age-associated genetic alterations in protein domains

泛癌分析揭示蛋白质结构域中与年龄相关的遗传变异

Category	Quartile
生物学	1
生物学, 遗传学	1

Pan-cancer analysis reveals age-associated genetic alterations in protein domains

ivySCI AI Smartly Parses PDF, Answers Researchers' Questions, and Helps You Understand Papers in Seconds

Journal Info

Category	Quartile
GENETICS & HEREDITY	1