Genomic characterization of therapy-associated polyposis reveals an alkylating mutational signature from prior treatment
Yashika Parashar, Zsofia Sztupinszki, Aurel György Prósz, Xiaolu Wang, Pratyusha Bala, Shweta Cavale, Chinedu Ukaegbu, Sapna Syngal, Asaf Maoz, Leah Biller, Ramona Lim, Matthew B. Yurgelun, Zoltan Szallasi, Nilay S. Sethi
Yashika Parashar, Zsofia Sztupinszki, Aurel György Prósz, Xiaolu Wang, Pratyusha Bala, Shweta Cavale, Chinedu Ukaegbu, Sapna Syngal, Asaf Maoz, Leah Biller, Ramona Lim, Matthew B. Yurgelun, Zoltan Szallasi, Nilay S. Sethi
View: Text | PDF
Research Letter Gastroenterology Oncology

Genomic characterization of therapy-associated polyposis reveals an alkylating mutational signature from prior treatment

Abstract

Authors

Yashika Parashar, Zsofia Sztupinszki, Aurel György Prósz, Xiaolu Wang, Pratyusha Bala, Shweta Cavale, Chinedu Ukaegbu, Sapna Syngal, Asaf Maoz, Leah Biller, Ramona Lim, Matthew B. Yurgelun, Zoltan Szallasi, Nilay S. Sethi

×

Figure 1

Clinicopathological and genomic analysis of patients with TAP.

Options: View larger image (or click on image) Download as PowerPoint
Clinicopathological and genomic analysis of patients with TAP. (A) Prima...
(A) Primary cancer diagnoses in patients with TAP (n = 29). (B) Secondary cancer prevalence in the general population (>2 million survivors), CYAC survivors (n = 14,359), and patients with TAP (n = 29). **Melanoma; cholangiocarcinoma; AML; DLBCL; esophageal Ca; vocal cord SCC; osteochondroma; acoustic neuroma; mandibular schwannoma. (C) Distribution of polyp histologic subtypes in TAP (n = 15). (D) Copy number profiles across the GREM1 locus in HMPS, FAP, and TAP adenomas. (E) Structural variant burden in normal tissue and adenomas from FAP and TAP. The box-and-whisker plots depict the minimum and maximum values (whiskers), the upper and lower quartiles, and the median. (F and G) Single-base substitution (SBS) mutational signature analysis of TAP adenomas with (F) and without (G) matched germline controls. (H) Paired normal and TAP adenoma organoids showing morphology, differentiation, and expression of SOX9 and KRT20. Arrowheads represent organoids that are differentiating in normal and adenoma culture from a patient with TAP. Student’s t test. Error bars depict mean with SEM. PDx, primary diagnosis; Tx, treatment; Chemo, chemotherapy; Radio, radiotherapy; Sx, surgery; TC, transverse colon; DC, descending colon; CLL, chronic lymphocytic leukemia; RCC, renal cell carcinoma; SCC, squamous cell carcinoma.