Gene mutations associated with tandem duplicator phenotype

1. A method, comprising:

(a) calculating a tandem duplicator phenotype (TDP) score for a genome of a tumor sample obtained from a subject,

wherein the TDP score is calculated using the following equation:

TDP

⁢

score

=

-

∑

i

⁢

❘

"\[LeftBracketingBar]"

Obs

i

-

Exp

i

❘

"\[RightBracketingBar]"

TD

+

k

wherein tandem duplication (TD) is the total number of tandem duplications in the tumor sample, Obs i is the observed number of tandem duplications for each chromosome i in the genome, Exp i is the expected number of tandem duplications for each chromosome i in the genome, and k is 0.71;

(b) measuring a length distribution of tandem duplications in the tumor sample with a TDP score above a threshold value of zero (0);

(c) assigning to the tumor sample one of at least six TDP subtypes based on the length distribution of the tandem duplications, wherein the tumor sample is assigned a Group 1 TDP subtype, a Group 1/2mix TDP subtype, or a Group 1/3mix TDP subtype;

(d) identifying the subject as a candidate for a therapy that targets tumors comprising tandem duplications in PTEN, RB1, and/or NF1 based on the TDP subtype of the tumor sample; and

(e) administering to the subject a therapy that comprises a platinum-based agent and/or an alkylating agent.

2. The method of claim 1 , wherein the at least six TDP subtypes are selected from the group consisting of: Group 1 TDP subtype, Group 2 TDP subtype, Group 3 TDP subtype, Group 1/2mix TDP subtype, Group 1/3mix TDP subtype, and Group 2/3mix TDP subtype.

3. The method of claim 2 , wherein the Group 1 TDP subtype is assigned to a tumor sample that comprises tandem duplications having a length of about 11 kb, the Group 2 TDP subtype is assigned to a tumor sample that comprises tandem duplications having a length of about 231 kb, the Group 3 TDP subtype is assigned to a tumor sample that comprises tandem duplications having a length of about 1.7 Mb, the Group 1/2mix TDP subtype is assigned to a tumor sample that comprises tandem duplications having a length of about 11 kb and tandem duplications having a length of about 231 kb, the Group 1/3mix TDP subtype is assigned to a tumor sample that comprises tandem duplications having a length of about 11 kb and tandem duplications having a length of about 1.7 Mb, and the Group 2/3mix TDP subtype is assigned to a tumor sample that comprises tandem duplications having a length of about 231 kb and tandem duplications having a length of about 1.7 Mb.

4. The method of claim 1 , wherein the therapy modulates BRCA1 and/or p53 activity.