Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing

Jianjun Zhang; Junya Fujimoto; Jianhua Zhang; David C. Wedge; Xingzhi Song; Jiexin Zhang; Sahil Seth; Chi Wan Chow; Yu Cao; Curtis Gumbs; Kathryn A. Gold; Neda Kalhor; Latasha Little; Harshad Mahadeshwar; Cesar Moran; Alexei Protopopov; Huandong Sun; Jiabin Tang; Xifeng Wu; Yuanqing Ye; William N. William; J. Jack Lee; John V. Heymach; Waun Ki Hong; Stephen Swisher; Ignacio I. Wistuba; P. Andrew Futreal

doi:10.1126/science.1256930

Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing

Jianjun Zhang, Junya Fujimoto, Jianhua Zhang, David C. Wedge, Xingzhi Song, Jiexin Zhang, Sahil Seth, Chi Wan Chow, Yu Cao, Curtis Gumbs, Kathryn A. Gold, Neda Kalhor, Latasha Little, Harshad Mahadeshwar, Cesar Moran, Alexei Protopopov, Huandong Sun, Jiabin Tang, Xifeng Wu, Yuanqing YeWilliam N. William, J. Jack Lee, John V. Heymach, Waun Ki Hong, Stephen Swisher, Ignacio I. Wistuba, P. Andrew Futreal

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Abstract

Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied.We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.

Original language	English (US)
Pages (from-to)	256-259
Number of pages	4
Journal	Science
Volume	346
Issue number	6206
DOIs	https://doi.org/10.1126/science.1256930
State	Published - Oct 10 2014

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Zhang, J., Fujimoto, J., Zhang, J., Wedge, D. C., Song, X., Zhang, J., Seth, S., Chow, C. W., Cao, Y., Gumbs, C., Gold, K. A., Kalhor, N., Little, L., Mahadeshwar, H., Moran, C., Protopopov, A., Sun, H., Tang, J., Wu, X., ... Futreal, P. A. (2014). Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science, 346(6206), 256-259. https://doi.org/10.1126/science.1256930

Zhang, J, Fujimoto, J, Zhang, J, Wedge, DC, Song, X , Zhang, J, Seth, S, Chow, CW, Cao, Y, Gumbs, C, Gold, KA, Kalhor, N, Little, L, Mahadeshwar, H, Moran, C, Protopopov, A, Sun, H, Tang, J, Wu, X, Ye, Y, William, WN, Lee, JJ , Heymach, JV, Hong, WK, Swisher, S , Wistuba, II & Futreal, PA 2014, 'Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing', Science, vol. 346, no. 6206, pp. 256-259. https://doi.org/10.1126/science.1256930

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title = "Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing",

abstract = "Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied.We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.",

author = "Jianjun Zhang and Junya Fujimoto and Jianhua Zhang and Wedge, {David C.} and Xingzhi Song and Jiexin Zhang and Sahil Seth and Chow, {Chi Wan} and Yu Cao and Curtis Gumbs and Gold, {Kathryn A.} and Neda Kalhor and Latasha Little and Harshad Mahadeshwar and Cesar Moran and Alexei Protopopov and Huandong Sun and Jiabin Tang and Xifeng Wu and Yuanqing Ye and William, {William N.} and Lee, {J. Jack} and Heymach, {John V.} and Hong, {Waun Ki} and Stephen Swisher and Wistuba, {Ignacio I.} and Futreal, {P. Andrew}",

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AU - Zhang, Jianjun

AU - Fujimoto, Junya

AU - Zhang, Jianhua

AU - Wedge, David C.

AU - Song, Xingzhi

AU - Zhang, Jiexin

AU - Seth, Sahil

AU - Chow, Chi Wan

AU - Cao, Yu

AU - Gumbs, Curtis

AU - Gold, Kathryn A.

AU - Kalhor, Neda

AU - Little, Latasha

AU - Mahadeshwar, Harshad

AU - Moran, Cesar

AU - Protopopov, Alexei

AU - Sun, Huandong

AU - Tang, Jiabin

AU - Wu, Xifeng

AU - Ye, Yuanqing

AU - William, William N.

AU - Lee, J. Jack

AU - Heymach, John V.

AU - Hong, Waun Ki

AU - Swisher, Stephen

AU - Wistuba, Ignacio I.

AU - Futreal, P. Andrew

PY - 2014/10/10

Y1 - 2014/10/10

N2 - Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied.We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.

AB - Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied.We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.

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Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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