Kyle Walsh

Overview:

Dr. Walsh’s research program focuses on genetic and epigenetic factors contributing to cancer predisposition in children and adults, with a special interest in brain tumors. This research is informed by both epidemiology and anthropological genetics, with computational work stressing statistical methodologies for “gene hunting” (e.g. GWAS, fine-mapping, admixture mapping, whole-genome sequencing). The laboratory engages in functional genomics research, investigating the biological impact of genetic variants linked to cancer risk, with a particular focus on regulation of telomere maintenance in pre-malignant cells. 

Positions:

Associate Professor of Neurosurgery

Neurosurgery
School of Medicine

Associate Professor in Population Health Sciences

Population Health Sciences
School of Medicine

Associate Professor in Pediatrics

Pediatrics, Children's Health Discovery Institute
School of Medicine

Associate Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2011

Yale University School of Medicine

Grants:

Genetic Susceptibility to Pediatric Glioma in Individuals and Diverse populations

Administered By
Neurosurgery
Awarded By
University of Southern California
Role
Principal Investigator
Start Date
End Date

The role of rare and common variants in genetic predisposition to medulloblastoma

Administered By
Neurosurgery
Awarded By
Sontag Foundation
Role
Principal Investigator
Start Date
End Date

Genetic Susceptibility to pediatric Osteosarcoma and Interaction with Measures of Childhood Growth

Administered By
Neurosurgery
Role
Principal Investigator
Start Date
End Date

Immune Correlates and Mechanisms of Perinatal Cytomegalovirus Infection and Later Life ALL Development

Administered By
Pediatrics, Children's Health Discovery Institute
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Genetic Susceptibility to Pediatric Glioma in Individuals and Diverse populations

Administered By
Neurosurgery
Awarded By
University of Southern California
Role
Principal Investigator
Start Date
End Date

Publications:

Performance of a nomogram for IDH-wild-type glioblastoma patient survival in an elderly cohort

MLA Citation
Shen, Erica, et al. “Performance of a nomogram for IDH-wild-type glioblastoma patient survival in an elderly cohort.” Neuro Oncology Advances, vol. 1, no. 1, Oxford University Press (OUP), May 2019. Crossref, doi:10.1093/noajnl/vdz036.
URI
https://scholars.duke.edu/individual/pub1437619
Source
crossref
Published In
Neuro Oncology Advances
Volume
1
Published Date
DOI
10.1093/noajnl/vdz036

Telomere Attrition in Childhood Cancer Survivors.

Childhood cancer survivors experience substantial treatment-related morbidity and biomarkers of long-term survivor health are needed. Leukocyte telomere length is shortened in childhood cancer survivors and associates with the occurrence of numerous chronic health conditions. Healthy lifestyle factors can attenuate telomere attrition in young-adult survivors, implicating critical windows for intervention.See related article by Song et al., p. 2362.
Authors
MLA Citation
Walsh, Kyle M. “Telomere Attrition in Childhood Cancer Survivors.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 26, no. 10, May 2020, pp. 2281–83. Epmc, doi:10.1158/1078-0432.ccr-20-0380.
URI
https://scholars.duke.edu/individual/pub1437618
PMID
32198150
Source
epmc
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
26
Published Date
Start Page
2281
End Page
2283
DOI
10.1158/1078-0432.ccr-20-0380

Germline variants in predisposition genes in children with Down syndrome and acute lymphoblastic leukemia.

Authors
Winer, P; Muskens, IS; Walsh, KM; Vora, A; Moorman, AV; Wiemels, JL; Roberts, I; Roy, A; de Smith, AJ
MLA Citation
Winer, Peleg, et al. “Germline variants in predisposition genes in children with Down syndrome and acute lymphoblastic leukemia.Blood Adv, vol. 4, no. 4, Feb. 2020, pp. 672–75. Pubmed, doi:10.1182/bloodadvances.2019001216.
URI
https://scholars.duke.edu/individual/pub1433297
PMID
32084258
Source
pubmed
Published In
Blood Adv
Volume
4
Published Date
Start Page
672
End Page
675
DOI
10.1182/bloodadvances.2019001216

Germline cancer predisposition variants and pediatric glioma: a population-based study in California.

BACKGROUND: Pediatric astrocytoma constitutes a majority of malignant pediatric brain tumors. Previous studies that investigated pediatric cancer predisposition have primarily been conducted in tertiary referral centers and focused on cancer predisposition genes. In this study, we investigated the contribution of rare germline variants to risk of malignant pediatric astrocytoma on a population level. METHODS: DNA samples were extracted from neonatal dried bloodspots from 280 pediatric astrocytoma patients (predominantly high grade) born and diagnosed in California and were subjected to whole-exome sequencing. Sequencing data were analyzed using agnostic exome-wide gene-burden testing and variant identification for putatively pathogenic variants in 175 a priori candidate cancer-predisposition genes. RESULTS: We identified thirty-three putatively pathogenic germline variants among 31 patients (11.1%) which located in 24 genes largely involved in DNA repair and cell cycle control. Patients with pediatric glioblastoma were most likely to harbor putatively pathogenic germline variants (14.3%, N=9/63). Five variants were located in TP53, of which four were identified among patients with glioblastoma (6.3%, N=4/63). The next most frequently mutated gene was NF1, in which putatively pathogenic variants were identified in four astrocytoma NOS patients. Gene-burden testing also revealed that putatively pathogenic variants in TP53 were significantly associated with pediatric glioblastoma on an exome-wide level (OR:32.8, p=8.04×10-7). CONCLUSION: A considerable fraction of pediatric glioma patients, especially those of higher grade, harbor a putatively pathogenic variant in a cancer predisposition gene. Some of these variants may be clinically actionable or may warrant genetic counseling.
Authors
Muskens, IS; de Smith, AJ; Zhang, C; Hansen, HM; Morimoto, L; Metayer, C; Ma, X; Walsh, KM; Wiemels, JL
MLA Citation
Muskens, Ivo S., et al. “Germline cancer predisposition variants and pediatric glioma: a population-based study in California.Neuro Oncol, Jan. 2020. Pubmed, doi:10.1093/neuonc/noaa014.
URI
https://scholars.duke.edu/individual/pub1428392
PMID
31970404
Source
pubmed
Published In
Neuro Oncol
Published Date
DOI
10.1093/neuonc/noaa014

POT1 mutation spectrum in tumour types commonly diagnosed among POT1-associated hereditary cancer syndrome families.

BACKGROUND: The shelterin complex is composed of six proteins that protect and regulate telomere length, including protection of telomeres 1 (POT1). Germline POT1 mutations are associated with an autosomal dominant familial cancer syndrome presenting with diverse malignancies, including glioma, angiosarcoma, colorectal cancer and melanoma. Although somatic POT1 mutations promote telomere elongation and genome instability in chronic lymphocytic leukaemia, the contribution of POT1 mutations to development of other sporadic cancers is largely unexplored. METHODS: We performed logistic regression, adjusted for tumour mutational burden, to identify associations between POT1 mutation frequency and tumour type in 62 368 tumours undergoing next-generation sequencing. RESULTS: A total of 1834 tumours harboured a non-benign mutation of POT1 (2.94%), of which 128 harboured a mutation previously reported to confer familial cancer risk in the setting of germline POT1 deficiency. Angiosarcoma was 11 times more likely than other tumours to harbour a POT1 mutation (p=1.4×10-20), and 65% of POT1-mutated angiosarcoma had >1 mutations in POT1. Malignant gliomas were 1.7 times less likely to harbour a POT1 mutation (p=1.2×10-3) than other tumour types. Colorectal cancer was 1.2 times less likely to harbour a POT1 mutation (p=0.012), while melanoma showed no differences in POT1 mutation frequency versus other tumours (p=0.67). CONCLUSIONS: These results confirm a role for shelterin dysfunction in angiosarcoma development but suggest that gliomas arising in the context of germline POT1 deficiency activate a telomere-lengthening mechanism that is uncommon in gliomagenesis.
Authors
Shen, E; Xiu, J; Lopez, GY; Bentley, R; Jalali, A; Heimberger, AB; Bainbridge, MN; Bondy, ML; Walsh, KM
MLA Citation
Shen, Erica, et al. “POT1 mutation spectrum in tumour types commonly diagnosed among POT1-associated hereditary cancer syndrome families.J Med Genet, Jan. 2020. Pubmed, doi:10.1136/jmedgenet-2019-106657.
URI
https://scholars.duke.edu/individual/pub1428973
PMID
31937561
Source
pubmed
Published In
Journal of Medical Genetics
Published Date
DOI
10.1136/jmedgenet-2019-106657