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Albert de la Chapelle (1933–2020)

2021; Elsevier BV; Volume: 108; Issue: 2 Linguagem: Inglês

10.1016/j.ajhg.2021.01.004

1537-6605

Amanda E. Toland, Heather Hampel,

Cancer Genomics and Diagnostics

Albert de la Chapelle, MD, PhD died of pneumonia on December 10, 2020 at the age of 87 in his beloved Finland. Dr. de la Chapelle was born on February 11, 1933 in Tenala, Finland and was named for his grandfather, a pediatrician. Following in his grandfather’s footsteps, he received a medical degree in 1957 from the University of Helsinki and was later board certified in internal medicine. In 1959, during his medical training, he read a paper by one of his professors linking Turner syndrome with monosomy X. This study highlighted the importance of research in understanding genetic conditions, and it piqued his curiosity. Dr. de la Chapelle pivoted away from practicing medicine to pursue a PhD and conduct his own research in the cytogenetics of sex determination. In 1962, he earned his PhD in Human Genetics with a thesis project focusing on Turner syndrome. Continuation of this research led him to the identification and characterization of additional sex chromosome disorders, including 46,XX sex reversal 1 (MIM: 400045), which is commonly referred to as de la Chapelle syndrome.1de la Chapelle A. Hortling H. Niemi M. Wennström J. XX sex chromosomes in a human male: first case.Acta Med. Scand. Suppl. 1964; 412: 25-38Google Scholar Post-graduate training included 2 years in the laboratory of Dr. Paul Marks at Columbia University and a year with Dr. Jean-Claude Kaplan at the University of Paris from 1981–1982. Over the next 20 years, Dr. de la Chapelle continued to conduct research on the sex chromosomes with seminal findings describing X,X males, providing evidence on recombination between the two chromosomes and identifying the pseudoautosomal regions on the X and Y chromosomes.2Rowley J.D. 2002 William Allen Award address. Introductory speech for Albert de la Chapelle.Am. J. Hum. Genet. 2003; 72: 233-235Abstract Full Text Full Text PDF PubMed Google Scholar His discoveries impacted not only our scientific understanding of the genetics of sex determination but also our social practices. In the 1980s, Dr. de la Chapelle was one of multiple scientists who stood up to the International Olympic Committee (IOC) for their use of sex chromosome and PCR-based tests to confirm the gender of Olympic athletes.3de la Chapelle A. The use and misuse of sex chromatin screening for ‘gender identification’ of female athletes.JAMA. 1986; 256: 1920-1923Crossref PubMed Scopus (46) Google Scholar From 1968 until 1998, the tests used by the IOC misidentified women with certain sex chromosome anomalies or mutations as male, resulting in great stigma and unfair practices to individuals incorrectly labeled (see “Web resources”). Because Dr. de la Chapelle was not ready to retire at the age of 65 (the mandatory retirement age in Finland) and his wife, Clara Bloomfield, MD, was across the Atlantic Ocean in the US, he decided to relocate to be with her. In 1997, he and Clara, a powerhouse in her own right in leukemia and lymphoma translational research, were recruited to the Ohio State University (OSU): she as Director of the Cancer Center and the James and Solove Research Institute and he as the inaugural director of a new translational research program in human cancer genetics. His academic home was the Department of Medical Genetics, Virology and Immunology (now Cancer Biology & Genetics) in which he was a Distinguished University Professor and the Leonard Immke Chair of Cancer Genetics. From this position, he developed a clinical Cancer Genetics Program staffed with genetic counselors and physicians. This program is now part of the Division of Human Genetics in the Department of Internal Medicine. Over the next 23 years, he also actively participated in growing an internationally recognized Cancer Genetics Program at the OSU Comprehensive Cancer Center. Dr. de la Chapelle was a trailblazer in the field of human genetics. In Finland, he was the first professor of Medical Genetics and directed the first medical cytogenetic lab. His genetics research continued with key discoveries about genes that underlie recessive disorders more prevalent in the Finish population (see “Web resources”). In the early 1990s, he began studies to understand the genetics of Lynch syndrome (MIM: 120435), a hereditary colorectal cancer syndrome. His group was the first to discover microsatellite instability in tumors of individuals with Lynch syndrome and to link the syndrome to MSH2 mutations.4Peltomäki P. Aaltonen L.A. Sistonen P. Pylkkänen L. Mecklin J.P. Järvinen H. Green J.S. Jass J.R. Weber J.L. Leach F.S. et al.Genetic mapping of a locus predisposing to human colorectal cancer.Science. 1993; 260: 810-812Crossref PubMed Scopus (798) Google Scholar Capitalizing on the unique tumor characteristics of Lynch syndrome-associated tumors, he led tumor screening studies of patients from Finland and Ohio with colorectal and endometrial cancers. These studies revealed that 3%–5% of all newly diagnosed colorectal and endometrial cancers are due to Lynch syndrome.5Hampel H. Frankel W.L. Martin E. Arnold M. Khanduja K. Kuebler P. Nakagawa H. Sotamaa K. Prior T.W. Westman J. et al.Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer).N. Engl. J. Med. 2005; 352: 1851-1860Crossref PubMed Scopus (1065) Google Scholar His work led to universal screening of nearly all colorectal and endometrial tumors for Lynch syndrome markers and downstream cascade genetic testing of family members of probands with intensive follow-up of individuals with inherited pathogenic variants. His work came full circle in 2015 when he co-authored a landmark paper showing that tumors with microsatellite instability respond well to immune checkpoint inhibitor therapy. This resulted in the first tumor agnostic FDA-approval of immunotherapy for microsatellite unstable tumors. Collectively, his discoveries have saved the lives of many individuals with Lynch syndrome. Since the early 2000s, Dr. de la Chapelle put considerable effort into understanding genetic susceptibility to thyroid cancer. He was a major contributor to three international genome-wide association studies (GWASs) that identified a critical functional role for long non-coding RNAs (lncRNAs) in thyroid cancer heritability, including identification of several new lncRNA genes that he functionally characterized. He led studies creating and validating polygenic risk scores for thyroid cancer and identified rare high susceptibility genes in families with autosomal dominant papillary thyroid cancer. He published seminal studies in identifying microRNA patterns in papillary thyroid cancer that provided the basis for some of the current molecular testing of thyroid nodules. During this time, Dr. de la Chapelle also participated in and led collaborative studies on the genetic susceptibility to acute myeloid leukemia (AML). Together with his wife, Clara, and in close collaboration with his friend Julius Gudmondson at deCODE in Iceland, he spearheaded the first large-scale GWAS in AML that led to the identification of a polymorphism near BRD4-interacting chromatin-remodeling complex-associated protein (BICRA) as an AML risk variant. He discovered the BAALC, whose high expression is associated with poor AML outcomes, as well as several AML-associated microRNAs. He also remained actively involved in the studies of recurrent chromosomal abnormalities and the identification of leukemia-associated genes and gene mutations. In addition to his studies in AML, he also passionately studied chronic lymphocytic leukemia (CLL) with special focus on the discovery of predisposing genes and variants in individual families and large patient cohorts. One of these studies conducted with Dr. Christoph Plass identified epigenetic silencing of DAPK1 through promoter methylation in almost all sporadic CLL cases. Dr. de le Chapelle received numerous prestigious awards and honors for the pivotal scientific contributions he made across his lifetime.6Printz C. First person profile: Albert de la Chapelle, MD, PhD: Known for several pioneering discoveries in genetics, Dr. de la Chapelle is working to shed light on the genes that cause thyroid cancer.Cancer. 2019; 125: 3285-3286Crossref PubMed Scopus (0) Google Scholar In 1997, he became a member of the National Academy of Science for his work in linkage and positional cloning to identify genes involved in Mendelian disorders. He received the William Allan Award from the American Society of Human Genetics in 2002 for substantial lifetime contributions to the fields of human and medical genetics. In Finland, he was honored by membership to its senior Academy of Sciences on Letters and was named a fellow in the Academy of Finland. He was also a Member of the Royal Swedish Academy of Sciences. In 2017, the Collaborative Group of the Americas on Inherited Colorectal Cancer awarded him a lifetime achievement award for his seminal contributions to our understanding of Lynch syndrome. Mentoring trainees was important to Dr. de la Chapelle. Over his lifetime, he mentored more than 100 scientists, including clinical fellows, postdoctoral fellows, graduate students, and undergraduate students. He served as an “unofficial” mentor to countless genetic counselors and junior faculty members. As a sign of his outstanding mentoring, many of mentees, including Drs. Juha Kere, Lauri Aaltonen, Ralf Krahe, Laura Valle, Paivi Peltomaki, Hidewaki Nakagawa, Christoph Plass, Natalia Pellegata, and Krystian Jazdzewski, have themselves become scientific leaders in genetics research. Dr. de la Chapelle’s mentorship was a true reflection of his personality. One of his recent mentees, Dr. Ann-Kathrin Eisfeld, describes his mentorship, “It would be first of all his unconditional friendship and support for the fellow as a person, and for their scientific ideas and goals, from big to small. It would be his unstoppable curiosity, which included lively discussions about the smallest details of geographic points and local traditions from the fellows’ hometowns, and, of course, his curiosity for everything in science and biology, even if it was far off his own research interest. Finally, it would be his unparalleled ability to see the big picture, find the one small detail that matters, and think big in every project.” He was known to state his honest opinion on matters in “the most charming way.” Many will remember him as a consummate gentleman, drinking his coffee in a proper china coffee cup with a saucer and referring to colleagues, trainees, and co-workers in conversation by Doctor, Professor, Ms., Mrs., or Mr. Dr. de la Chapelle was dedicated to the arts and purchased artwork of multiple genres for his homes in the US and Finland. He admired and collected old silver pieces, especially from Germany, France, and Poland, which he displayed in his home for everybody to admire during gatherings of fellows and friends and during holidays. In 2005, he established a fund to support the Swedish Literacy Society of Finland, which purchased art for the Västra Nylands museum, part of the art museum Ekta in Ekenäs (see “Web resources”). In 2017, in collaboration with his wife, he started the Albert de la Chapelle Art Foundation with a goal of building a new art museum next to the Ekta Museum in Raseborg. In addition to art, Dr. de la Chapelle also collected other things, including Scrooge McDucks and singing stuffed animals (especially Kermit the Frog and Miss Piggy). Outside of the laboratory and art world, Dr. de la Chapelle enjoyed the outdoors. As a youth, he excelled in Skeet-shooting and represented Finland in multiple World Cups (see “Web resources”). Despite living in the US for over 20 years, he remained a Finn, spending a portion of his summer there every year. He loved to go fishing and take long walks to collect mushrooms and berries. In Ohio, he enjoyed taking care of his garden, including an annual planting of hundreds of daffodils. Dr. de la Chapelle was preceded in death in early 2020 by his beloved wife, Clara. We are extraordinarily fortunate to have worked with such a prominent scientific leader in Human Genetics. As colleagues of his in the Department of Cancer Biology and Genetics, the Division of Human Genetics, the Human Cancer Genetics Program that he founded, the Cancer Biology Program, and across OSU, we will also remember him fondly for his mentorship and for inspiring many of us to follow him to better understand the role that Genetics plays in human disease. We thank Matthew Ringel, Ann-Kathrin Eisfeld, and faculty in the Department of Cancer Biology and Genetics and the Division of Human Genetics for providing suggestions and stories of their interactions with Dr. de la Chapelle. Albert de la Chapelle, https://en.wikipedia.org/wiki/Albert_de_la_ChapelleAlbert de la Chapelle - här är mannen som vill donera ett konstmuseum till Raseborg, https://svenska.yle.fi/artikel/2020/11/08/albert-de-la-chapelle-har-ar-mannen-som-vill-donera-ett-konstmuseum-till-raseborg?fbclid=IwAR3Az3Qh66ssIM25sxDAcOhlQKM9Xx0tT-1UKSKWbOoxLKSsxFmZjaO9rtkOMIM, https://omim.org/